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by Keyword: acid

Castrejón-Comas, V, Mataró, N, Resina, L, Zanuy, D, Nuñez-Aulina, Q, Sánchez-Morán, J, Enshaei, H, Arnau, M, Muñoz-Galán, H, Worch, JC, Dove, AP, Alemán, C, Pérez-Madrigal, MM, (2025). Electro-responsive hyaluronic acid-based click-hydrogels for wound healing Carbohydrate Polymers 348, 122941

With the aim of healing challenging skin wounds, electro-responsive click-hydrogels made of hyaluronic acid (clickHA) crosslinked with a modified polyethylene glycol precursor (PEG) were prepared by semi- interpenetrating a conducting polymer, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) by oxidative polymerization. The porosity and pore size of the mixed hydrogel, clickHA/PEDOT-MeOH, were both higher than those determined for the hydrogel without PEDOT-MeOH, while a honeycomb-like morphology with PEDOT-MeOH covering the pore walls was observed. Although such PEDOT-MeOH-induced changes did not influence the water absorption capacity of clickHA, they drastically affected the mechanical and electrochemical behavior. More specifically, the semi-interpenetration of PEDOT-MeOH into clickHA resulted in an increase of the Young's modulus, the compressive strength and, especially, the electrochemical activity. The biocompatibility and the potential for skin regeneration of clickHA/PEDOT-MeOH were preliminary assessed using viability and wound-healing assays with epithelial cells. Not only is the conducting hydrogel formulation biocompatible, but also promotes efficient cell migration by electrostimulation using a small voltage (0.5 V) for a short time (15 min). Thus, in just 1 h the wound gap was repaired, and a homogeneous monolayer of migrated cells was formed.

JTD Keywords: 4-ethylenedioxythiophene, Car, Click hydrogel, Conducting polymer, Hyaluronic acid, Poly(3, Proliferation, Rational design, Scaffold, Skin, Wound dressing


Fontana-Escartín, A, Bertran, O, Alemán, C, (2024). Materials engineering in electrochemical biosensors: A review of cost-effective approaches to efficient biodetection Materials Today Communications 41, 111030

Electrochemical sensors are sophisticated devices capable of detecting a wide range of chemical compounds with exceptional sensitivity and efficiency. Their importance is particularly pronounced in biomedical applications, where the rapid and accurate detection of biomolecules such as dopamine (DA), glucose (G), and nicotinamide adenine dinucleotide (NADH) is crucial for early diagnosis and disease management. These biomarkers are key in monitoring and managing conditions like diabetes, Parkinson and Alzheimer diseases, and bacterial infections. This review provides a comprehensive overview of electrochemical biosensors, detailing the methodologies commonly used by researchers and the latest technological advancements that enable more efficient device development. In this regard, the focus is on the impact and trends of various materials utilized in the fabrication of electrochemical biosensors, including conducting polymers, ceramics, and carbon-based materials. By examining the state of the art, we explore how these materials contribute to enhanced performance and reliability. Furthermore, while the development of highly selective and sensitive nanocomposites has been a primary focus in the field, this review also highlights efforts toward creating cost-effective biosensors with rapid prototyping capabilities. Such innovations aim to maintain high efficacy in electrochemical detection while making advanced diagnostics more accessible. In conclusion, this study aims to inform researchers and professionals about the evolving materials landscape in electrochemical biosensing, offering insights into the future directions of this critical technology.

JTD Keywords: Biomolecules, Biosensor, Dopamine, Electroactive materials, Electrochemical sensors, Electrode, Glucose biosensor, Nanoparticles, Nanosheets, Oxidas, Sensor, Temperature, Transition-metal carbides, Uric-acid


Ximenes-Carballo, Celia, Rey-Vinolas, Sergi, Blanco-Fernandez, Barbara, Perez-Amodio, Soledad, Engel, Elisabeth, Castano, Oscar, (2024). Combining three-dimensionality and CaP glass-PLA composites: Towards an efficient vascularization in bone tissue healing Biomaterials Advances 164, 213985

Bone regeneration often fails due to implants/grafts lacking vascular supply, causing necrotic tissue and poor integration. Microsurgical techniques are used to overcome this issue, allowing the graft to anastomose. These techniques have limitations, including severe patient morbidity and current research focuses on stimulating angiogenesis in situ using growth factors, presenting limitations, such as a lack of control and increased costs. Non-biological stimuli are necessary to promote angiogenesis for successful bone constructs. Recent studies have reported that bioactive glass dissolution products, such as calcium-releasing nanoparticles, stimulate hMSCs to promote angiogenesis and new vasculature. Moreover, the effect of 3D microporosity has also been reported to be important for vascularisation in vivo. . Therefore, we used room-temperature extrusion 3D printing with polylactic acid (PLA) and calcium phosphate (CaP) based glass scaffolds, focusing on geometry and solvent displacement for scaffold recovery. Combining both methods enabled reproducible control of 3D structure, porosity, and surface topography. Scaffolds maintained calcium ion release at physiological levels and supported human mesenchymal stem cell proliferation. Scaffolds stimulated the secretion of vascular endothelial growth factor (VEGF) after 3 days of culture. Subcutaneous implantation in vivo indicated good scaffold integration and blood vessel infiltration as early as one week after. PLA-CaP scaffolds showed increased vessel maturation 4 weeks after implantation without vascular regression. Results show PLA/CaP-based glass scaffolds, made via controlled 3D printing, support angiogenesis and vessel maturation, promising improved vascularization for bone regeneration.

JTD Keywords: 3d-printed porosity, Angiogenic growth-factors, Bioceramic scaffolds, Bone angiogenesis, Calcium phosphat, Calcium-phosphate, Cells, Composite, Extracellular calcium, Functional-role, In-vitro, Inorganic trace-elements, Matri, Polylactic acid, Regeneration


Barcelona-Estaje, E, Oliva, MAG, Cunniffe, F, Rodrigo-Navarro, A, Genever, P, Dalby, MJ, Roca-Cusachs, P, Cantini, M, Salmeron-Sanchez, M, (2024). N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity Nature Communications 15, 8824

Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment. The crosstalk between cell-cell and cell-matrix adhesions regulates stem cell fate. Here, the authors reveal a critical role for matrix viscosity in controlling this crosstalk, which they explain via a modified molecular clutch model.

JTD Keywords: Actin cytoskeleton, Adhesion, Animals, Arginyl-glycyl-aspartic acid, Cadherins, Cell adhesion, Cell communication, Fibronectin, Force transmission, Humans, Hydrogel, Integrins, Lipid bilayers, Matrix, Mechanotransduction, Mechanotransduction, cellular, Mesenchymal stem cells, Mobility, Oligopeptides, Osteogenic differentiation, Substrate stiffness, Vinculin, Viscosity


Fraire JC, Prado-Morales C, Aldaz Sagredo A, Caelles AG, Lezcano F, Peetroons X, Bakenecker AC, Di Carlo V, Sánchez S, (2024). Swarms of Enzymatic Nanobots for Efficient Gene Delivery Acs Applied Materials & Interfaces 16, 47192-47205

This study investigates the synthesis and optimization of nanobots (NBs) loaded with pDNA using the layer-by-layer (LBL) method and explores the impact of their collective motion on the transfection efficiency. NBs consist of biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and are powered by the urease enzyme, enabling autonomous movement and collective swarming behavior. In vitro experiments were conducted to validate the delivery efficiency of fluorescently labeled NBs, using two-dimensional (2D) and three-dimensional (3D) cell models: murine urothelial carcinoma cell line (MB49) and spheroids from human urothelial bladder cancer cells (RT4). Swarms of pDNA-loaded NBs showed enhancements of 2.2- to 2.6-fold in delivery efficiency and 6.8- to 8.1-fold in material delivered compared to inhibited particles (inhibited enzyme) and the absence of fuel in a 2D cell culture. Additionally, efficient intracellular delivery of pDNA was demonstrated in both cell models by quantifying and visualizing the expression of eGFP. Swarms of NBs exhibited a >5-fold enhancement in transfection efficiency compared to the absence of fuel in a 2D culture, even surpassing the Lipofectamine 3000 commercial transfection agent (cationic lipid-mediated transfection). Swarms also demonstrated up to a 3.2-fold enhancement in the amount of material delivered in 3D spheroids compared to the absence of fuel. The successful transfection of 2D and 3D cell cultures using swarms of LBL PLGA NBs holds great potential for nucleic acid delivery in the context of bladder treatments.

JTD Keywords: Animals, Barrier, Cell line, tumor, Dna, Drug delivery, Drug-delivery, Enzyme catalysis, Gene delivery, Gene transfer techniques, Humans, Lactic acid, Mice, Nanobots, Nanoparticles, Pdna, Plasmids, Polyglycolic acid, Polylactic acid-polyglycolic acid copolymer, Swarming, Transfectio, Transfection, Urease, Urinary bladder neoplasms


Oliver-Cervelló, L, López-Gómez, P, Martin-Gómez, H, Marion, M, Ginebra, MP, Mas-Moruno, C, (2024). Functionalization of Alginate Hydrogels with a Multifunctional Peptide Supports Mesenchymal Stem Cell Adhesion and Reduces Bacterial Colonization Chemistry-A European Journal 30, e202400855

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1-11 region of lactoferrin (LF). The RGD-LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide-functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram-positive and Gram-negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels. In this work we report on the functionalization of an alginate hydrogel with a tailor-made multifunctional peptide containing the cell adhesive RGD motif and the LF1-11 antibacterial peptide. Such novel multifunctional biomaterial ensures the viability of human mesenchymal stem cells, enhances ALP activity and decreases bacterial infections of both Gram-positive and Gram-negative models. image

JTD Keywords: Alginate hydrogel, Alginates, Anti-bacterial agents, Antimicrobial peptid, Antimicrobial peptide, Antimicrobial peptides, Arginyl-glycyl-aspartic acid, Biocompatible materials, Biofunctionalization, Bone, Cell adhesion, Cell survival, Composite hydrogels, Cross-linking, Hlf1-11 peptide, Human lactoferrin, Humans, Hydrogels, Immobilization, Mesenchymal stem cells, Multifunctional peptide, Oligopeptides, Peptides, Physical-properties, Scaffolds, Surfac, Tissue engineering


Schofield, C, Sarrigiannidis, S, Moran-Horowich, A, Jackson, E, Rodrigo-Navarro, A, van Agtmael, T, Cantini, M, Dalby, MJ, Salmeron-Sanchez, M, (2024). An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis Advanced Healthcare Materials 13, e2303777

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions. The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Here a simple model of the BBB that allows culture of endothelial cells on growth-factor functionalised membranes is introduced. This novel in vitro model of the BBB offers a robust platform for studying key barriergenic biochemical factors influencing barrier formation without the use of the complicated co-culture conditions. image

JTD Keywords: Animals, Bbb, Blood-brain barrier, Densit, Differentiation, Ecm, Electrospinning, Endothelial cells, Endothelial-cell lines, Expression, Fiber diameter, Fibroblast-growth-factor, Growth factors, Humans, In vitro mode, In vitro model, Membranes, artificial, Models, biological, Morphology, Permeability, Poly(l-lactic acid), Poly(lactide), Polyesters, Proteins


Colombi, S, Sáez, I, Borras, N, Estrany, F, Pérez-Madrigal, MM, García-Torres, J, Morgado, J, Alemán, C, (2024). Glyoxal crosslinking of electro-responsive alginate-based hydrogels: Effects on the properties Carbohydrate Polymers 337, 122170

To improve the features of alginate-based hydrogels in physiological conditions, Ca2+-crosslinked 2 +-crosslinked semi interpenetrated hydrogels formed by poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid and alginate (PEDOT/Alg) were subjected to a treatment with glyoxal to form a dual ionic/covalent network. The covalent network density was systematically varied by considering different glyoxalization times (tG). t G ). The content of Ca2+ was significantly higher for the untreated hydrogel than for the glyoxalized ones, while the properties of the hydrogels were found to largely depend on t G . The porosity and swelling capacity decreased with increasing while the stiffness and electrical conductance retention capacity increased with t G . The potentiodynamic response of the hydrogels notably depended on the amount of conformational restraints introduced by the glyoxal, which is a very short crosslinker. Thus, the re-accommodation of the polymer chains during the cyclic potential scans became more difficult with increasing number of covalent crosslinks. This information was used to improve the performance of untreated PEDOT/Alg as electrochemical sensor of hydrogen peroxide by simply applying a tG G of 5 min. Overall, the control of the properties of glyoxalized hydrogels through tG G is very advantageous and can be used as an on-demand strategy to improve the performance of such materials depending on the application.

JTD Keywords: 4-ethylenedioxythiophene), Acid, Behavior, Cell, Conducting hydrogels, Dual networ, Electrochemical biosensor, Fabrication, Gel, Linke, Microspheres, Peroxidase, Poly(3, Polyvinyl-alcohol, Semi-interpenetrated hydrogel


Bernabeu, M, Prieto, A, Salguero, D, Miro, L, Cabrera-Rubio, R, Collado, MC, Hüttener, M, Pérez-Bosque, A, Juárez, A, (2024). Infection of mice by the enteroaggregative E. coli strain 042 and two mutant derivatives overexpressing virulence factors: impact on disease markers, gut microbiota and concentration of SCFAs in feces Scientific Reports 14, 16945

Several pathogenic Escherichia coli strains cause diarrhea. Enteroaggregative E. coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC cells form a "stacked-brick" arrangement over the intestinal epithelial cells. EAEC isolates express, among other virulence determinants, the AggR transcriptional activator and the aggregative adherence fimbriae (AAF). Overexpression of the aggR gene results in increased expression of virulence factors such as the aff genes, as well as several genes involved in specific metabolic pathways such as fatty acid degradation (fad) and arginine degradation (ast). To support the hypothesis that induction of the expression of some of these pathways may play a role in EAEC virulence, in this study we used a murine infection model to evaluate the impact of the expression of these pathways on infection parameters. Mice infected with a mutant derivative of the EAEC strain 042, characterized by overexpression of the aggR gene, showed increased disease symptoms compared to those exhibited by mice infected with the wild type (wt) strain 042. Several of these symptoms were not increased when the infecting mutant, which overexpressed aggR, lacked the fad and ast pathways. Therefore, our results support the hypothesis that different metabolic pathways contribute to EAEC virulence.

JTD Keywords: Adherence, Aggr, Burde, Chain fatty-acids, Children, Enteroaggregative e. coli, Escherichia-coli, Etiology, Infection, Mice, Microbiota, Persistent diarrhea, Protein, Scfa, Sex-differences


Longarzo, ML, Vázquez, RF, Bellini, MJ, Zamora, RA, Redondo-Morata, L, Giannotti, MI, Oliveira, ON Jr, Fanani, ML, Maté, SM, (2024). Understanding the effects of omega-3 fatty acid supplementation on the physical properties of brain lipid membranes Iscience 27, 110362

A deficiency in omega-3 fatty acids ( to 3 FAs) in the brain has been correlated with cognitive impairment, learning deficiencies, and behavioral changes. In this study, we provided to 3 FAs as a supplement to spontaneously hypertensive rats (SHR+ to 3). Our focus was on examining the impact of dietary supplementation on the physicochemical properties of the brain-cell membranes. Significant increases in to 3 levels in the cerebral cortex of SHR+ to 3 were observed, leading to alterations in brain lipid membranes molecular packing, elasticity, and lipid miscibility, resulting in an augmented phase disparity. Results from synthetic lipid mixtures confirmed the disordering effect introduced by to 3 lipids, showing its consequences on the hydration levels of the monolayers and the organization of the membrane domains. These findings suggest that dietary to 3 FAs influence the organization of brain membranes, providing insight into a potential mechanism for the broad effects of dietary fat on brain health and disease.

JTD Keywords: Behavio, Bilayers, Docosahexaenoic acid, Metabolism, Molecular packing, Phosphatidylcholine, Phosphatidylethanolamine, Polyunsaturated fatty-acids, Raft, Spectroscopy, Sphingomyelin


Fonte, M, Rôla, C, Santana, S, Avalos-Padilla, Y, Fernàndez-Busquets, X, Prudèncio, M, Gomes, P, Teixeira, C, (2024). Disclosure of cinnamic acid/4,9-diaminoacridine conjugates as multi-stage antiplasmodial hits Bioorganic & Medicinal Chemistry 104, 117714

4,9-diaminoacridines with reported antiplasmodial activity were coupled to different trans-cinnamic acids, delivering a new series of conjugates inspired by the covalent bitherapy concept. The new compounds were more potent than primaquine against hepatic stages of Plasmodium berghei, although this was accompanied by cytotoxic effects on Huh-7 hepatocytes. Relevantly, the conjugates displayed nanomolar activities against blood stage P. falciparum parasites, with no evidence of hemolytic effects below 100 mu M. Moreover, the new compounds were at least 25-fold more potent than primaquine against P. falciparum gametocytes. Thus, the new antiplasmodial hits disclosed herein emerge as valuable templates for the development of multi-stage antiplasmodial drug candidates.

JTD Keywords: Acid-derivatives, Analogs, Antimalarial, Artemisinin, Bearing, Cinnamic acid, Covalent bitherapy, Diaminoacridine, Good health and well-being, Malaria, Multi-target, N-cinnamoylation, Plasmodium-falciparum, Primaquine, Quinacrine, Resistance


Ruiz-González, N, Esporrín-Ubieto, D, Hortelao, AC, Fraire, JC, Bakenecker, AC, Guri-Canals, M, Cugat, R, Carrillo, JM, Garcia-Batlletbó, M, Laiz, P, Patiño, T, Sánchez, S, (2024). Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media Small 20, 2309387

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods. The conceptual idea of the novel approach using hyaluronidase NMs (HyaNMs) to interact with and reduce the viscosity of the synovial fluid (SF) and urease NMs (UrNMs) for a more efficient transport of therapeutic agents in joints.image

JTD Keywords: Biological barrier, Clinical research, Clinical treatments, Collective motion, Collective motion,nanomotors,nanorobots,swarming,viscous medi, Collective motions, Complex networks, Enzymatic reaction, Enzymes, Hyaluronic acid, Hyaluronic-acid,ph,viscoelasticity,adsorption,barriers,behavior,ureas, Macromolecules, Medical nanotechnology, Nano robots, Nanomotors, Nanorobots, Swarming, Synovial fluid, Target location, Viscous media, Viscous medium


Ramirez-Alba, Maria Dolores, Molins-Martinez, Marta, Garcia-Torres, Jose, Romanini, Michela, Macovez, Roberto, Perez-Madrigal, Maria M, Aleman, Carlos, (2024). pH and electrically responsive hydrogels with adhesive property Reactive & Functional Polymers 196, 105841

Applications of sodium alginate (Alg) and polyacrylic acid (PAA) hydrogels in biomedicine are well-known. These are predefined by the strength and weakness of their properties, which in turn depend on the chemical structure and the architecture of their crosslinks. In this work, Alg biopolymer has been grafted to synthetic PAA that has been chemically crosslinked using N,N '-methylene-bisacrylamide (MBA) to produce a pH responsive hydrogel with adhesive property. The double crosslinking network, which combines MBA-mediated covalent crosslinks and ionic crosslinks in Alg domains, results in an elastic modulus that resembles that of highly anisotropic and viscoelastic human skin. After addressing the influence of the dual network onto the Alg-g-PAA hydrogel properties, a prospection of its potential as an adhesive has been made considering different surfaces (rubber, paper steel, porcine skin, etc). The bonding energy onto porcine skin, 32.6 +/- 4.6 J/m2, revealed that the Alg-g-PAA hydrogel can be proposed in the biomedical field as tissue adhesive for wound healing applications. Finally, the hydrogel has been semi-interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) chains through a chemical oxidative polymerization process. The resulting hydrogel, Alg-g- PAA/PEDOT-MeOH, which is even more porous than Alg-g-PAA, in addition to being electro-responsive, maintains adhesive properties.

JTD Keywords: Adhesion properties, Adhesion properties,biomedical applications,bonding energy,dual network,conducting hydrogel, Adhesive properties, Adhesives, Biomedical applications, Biopolymers, Bonding energies, Bonding energy, Chemical bonds, Conducting hydrogels, Crosslinking, Dual network, Hydrogels, Medical applications, Methylenebisacrylamide, Poly(acrylic acid), Porcine skin, Property, Rational design,film, Sodium alginate


Fontana-Escartín, A, Lanzalaco, S, Zhilev, G, Armelin, E, Bertran, O, Alemán, C, (2024). Oxygen plasma treated thermoplastics as integrated electroresponsive sensors Materials Today Communications 38, 107653

Polypropylene (PP), thermoplastic polyurethane (TPU), polyethylene terephthalate glycol (PETG) and polylactic acid (PLA) 3D printed specimens, which are intrinsically non-electroresponsive materials, have been converted into electroresponsive electrodes applying a low-pressure oxygen plasma treatment. After complete chemical, morphological and electrochemical characterization, plasma treated samples have been applied as integrated electrochemical sensors for detecting dopamine and serotonin by cyclic voltammetry and chronoamperometry. Results show differences in the sensing behavior, which have been explained on the basis of the chemical structure of the pristine materials. While plasma treated PLA exhibits the highest performance as electrochemical sensor in terms of sensitivity (lowest limits of detection and quantification) and selectivity (against uric acid and ascorbic acid as interfering substances), plasma treated PP displays the poorest behavior due to its low polarity compared to PLA 3D-printed electrodes. Instead, plasma treated TPU and PETG shows a very good response, much closer to PLA, as sensitive electrodes towards neurotransmitter molecules (dopamine and serotonin). Overall, results open a new door for the fabrication of electrochemical conductive sensors using intrinsically insulating materials, without the need of chemical functionalization processes.

JTD Keywords: 3d printing, Amines, Ascorbic acid, Chemical characterization, Cyclic voltammetry, Dopamine, Electrochemical characterizations, Electrochemical sensor s, Electrochemical sensors, Electrode materials, Electroresponsive materials, Low-pressure oxygen-plasma treatments, Morphological characterization, Multiwalled carbon nanotubes (mwcn), Neurophysiology, Oxygen, Oxygen plasmas, Plastic bottles, Polyethylene terephthalate glycol, Polyethylene terephthalate glycols, Polyethylene terephthalates, Polylact i c acid, Polylactic acid, Polylactic acid pla, Polyols, Polypropylene, Polypropylene oxides, Polypropylenes, Polyurethanes, Reinforced plastics, Supercapacitors, Thermoplast i c polyurethane, Thermoplastic polyurethane, Thermoplastic polyurethanes


Montcusí, B, Madrid-Gambin, F, Pozo, OJ, Marco, S, Marin, S, Mayol, X, Pascual, M, Alonso, S, Salvans, S, Jiménez-Toscano, M, Cascante, M, Pera, M, (2024). Circulating metabolic markers after surgery identify patients at risk for severe postoperative complications: a prospective cohort study in colorectal cancer International Journal Of Surgery 110, 1493-1501

Background: Early detection of postoperative complications after colorectal cancer (CRC) surgery is associated with improved outcomes. The aim was to investigate early metabolomics signatures capable to detect patients at risk for severe postoperative complications after CRC surgery. Materials and methods: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before and after surgery, and analyzed by mass spectrometry obtaining 188 metabolites and 21 ratios. Postoperative complications were registered with Clavien-Dindo Classification and Comprehensive Complication Index. Results: One hundred forty-six patients were included. Surgery substantially modified metabolome and metabolic changes after surgery were quantitatively associated with the severity of postoperative complications. The strongest positive relationship with both Clavien-Dindo and Comprehensive Complication Index (beta=4.09 and 63.05, P<0.001) corresponded to kynurenine/tryptophan, against an inverse relationship with lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs). Patients with LPC18:2/PCa36:2 below the cut-off 0.084 mu M/mu M resulted in a sevenfold higher risk of major complications (OR=7.38, 95% CI: 2.82-21.25, P<0.001), while kynurenine/tryptophan above 0.067 mu M/mu M a ninefold (OR=9.35, 95% CI: 3.03-32.66, P<0.001). Hexadecanoylcarnitine below 0.093 mu M displayed a 12-fold higher risk of anastomotic leakage-related complications (OR=11.99, 95% CI: 2.62-80.79, P=0.004). Conclusion: Surgery-induced phospholipids and amino acid dysregulation is associated with the severity of postoperative complications after CRC surgery, including anastomotic leakage-related outcomes. The authors provide quantitative insight on metabolic markers, measuring vulnerability to postoperative morbidity that might help guide early decision-making and improve surgical outcomes.

JTD Keywords: Acids, Anastomotic leakage, Bypass, Clinical-practice guidelines, Colon, Colorectal cancer, Metabolomics, Postoperative complications, Predict, Sepsis, Trauma, Tryptophan degradation


Humbert, P, Kampleitner, C, De Lima, J, Brennan, MA, Lodoso-Torrecilla, I, Sadowska, JM, Blanchard, F, Canal, C, Ginebra, MP, Hoffmann, O, Layrolle, P, (2024). Phase composition of calcium phosphate materials affects bone formation by modulating osteoclastogenesis Acta Biomaterialia 176, 417-431

Human mesenchymal stromal cells (hMSCs) seeded on calcium phosphate (CaP) bioceramics are extensively explored in bone tissue engineering and have recently shown effective clinical outcomes. In previous pre-clinical studies, hMSCs-CaP-mediated bone formation was preceded by osteoclastogenesis at the implantation site. The current study evaluates to what extent phase composition of CaPs affects the osteoclast response and ultimately influence bone formation. To this end, four different CaP bioceramics were used, hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) and two biphasic composites of HA/beta- TCP ratios of 60/40 and 20/80 respectively, for in vitro osteoclast differentiation and correlation with in vivo osteoclastogenesis and bone formation. All ceramics allowed osteoclast formation in vitro from mouse and human precursors, except for pure HA, which significantly impaired their maturation. Ectopic implantation alongside hMSCs in subcutis sites of nude mice revealed new bone formation at 8 weeks in all conditions with relative amounts for beta-TCP > biphasic CaPs > HA. Surprisingly, while hMSCs were essential for osteoinduction, their survival did not correlate with bone formation. By contrast, the degree of early osteoclastogenesis (2 weeks) seemed to define the extent of subsequent bone formation. Together, our findings suggest that the osteoclastic response could be used as a predictive marker in hMSC-CaPbased bone regeneration and strengthens the need to understand the underlying mechanisms for future biomaterial development. Statement of significance The combination of mesenchymal stromal cells (MSCs) and calcium phosphate (CaP) materials has demonstrated its safety and efficacy for bone regeneration in clinical trials, despite our insufficient understanding of the underlying biological mechanisms. Osteoclasts were previously suggested as key mediators between the early inflammatory phase following biomaterial implantation and the subsequent bone formation. Here we compared the affinity of osteoclasts for various CaP materials with different ratios of hydroxyapatite to beta-tricalcium phosphate. We found that osteoclast formation, both in vitro and at early stages in vivo, correlates with bone formation when the materials were implanted alongside MSCs in mice. Surprisingly, MSC survival did not correlate with bone formation, suggesting that the number or phenotype of osteoclasts formed was more important. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

JTD Keywords: Acid phosphatase tartrate resistant isoenzyme, Animal, Animal cell, Animal experiment, Animal tissue, Animals, Article, Beta-tricalcium phosphate, Bioceramics, Biocompatible materials, Biomaterial, Bone, Bone development, Bone formation, Bone regeneration, Calcium phosphate, Calcium phosphate materials, Calcium phosphates, Cd14 antigen, Cell differentiation, Cell engineering, Cell maturation, Cell survival, Ceramics, Chemical composition, Controlled study, Correlation analysis, Correlation coefficient, Data correlation, Durapatite, Engraftment, Flowcharting, Human, Human cell, Human mesenchymal stromal cell, Human mesenchymal stromal cells, Humans, Hydroxyapatite, Hydroxyapatites, In vitro study, In vivo study, In-vitro, In-vivo, Mammals, Marrow stromal cells, Material composition, Material compositions, Mesenchymal stroma cell, Mesenchymal stromal cells, Mice, Mice, nude, Monocyte, Mouse, Nonhuman, Nude mouse, Ossification, Osteoclast, Osteoclastogenesis, Osteoclasts, Osteogenesis, Osteoinduction, Phase composition, Regeneration strategies, Resorption, Scaffolds, Stem-cells, Subcutaneous tissue, Tissue engineering, Transmission control protocol, Tri-calcium phosphates, Vimentin


Mohammed-Sadhakathullah, AHM, Paulo-Mirasol, S, Molina, BG, Torras, J, Armelin, E, (2024). PLA-PEG-Cholesterol biomimetic membrane for electrochemical sensing of antioxidants Electrochimica Acta 476, 143716

Polymeric membranes exhibit unique and modulate transport properties when they are properly functionalised, which make them ideal for ions transport, molecules separation and molecules interactions. The present work proposes the design and fabrication of nanostructured membranes, composed by biodegradable poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), incorporating a lipophilic molecule (cholesterol) covalently bonded, were especially designed to provide even more application opportunities in sensors field. Electrochemical studies, by means of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV), revealed important differences regarding the functionalised and non-functionalised PLA systems. PEGcholesterol building block units showed a clear affinity with ascorbic acid (vitamin C) and Trolox (R) (a watersoluble analogue of vitamin E), both hydrophilic in nature, with a limit of detection capacity of 8.12 mu M for AA and 3.53 mu M for AA and Trolox, respectively, in aqueous salt solution. The bioinspired polymer may be used to incorporate antioxidant property that allow the design of anti-stress biosensors, electrodes for the detection of vitamin C or vitamin E in biomedical nutrition programs, among other applications.

JTD Keywords: Antioxidant molecules, Antioxidants, Application programs, Ascorbic acid, Biomimetics, C (programming language), Capacity, Chemical detection, Cholesterol, Cyclic voltammetry, Electrochemical detection, Electrochemical impedance spectroscopy, Functional polymers, Functionalized, Lactic acid, Molecules, Nanomembranes, Poly ethylene glycols, Poly lactic acid, Poly(ethylene glycol), Poly(ethyleneglycol), Poly(lactic acid), Polyethylene glycols, Vitamin-e


Rae, CD, Baur, JA, Borges, K, Dienel, G, Díaz-García, CM, Douglass, SR, Drew, K, Duarte, JMN, Duran, J, Kann, O, Kristian, T, Lee-Liu, D, Lindquist, BE, Mcnay, EC, Robinson, MB, Rothman, DL, Rowlands, BD, Ryan, TA, Scafidi, J, Scafidi, S, Shuttleworth, CW, Swanson, RA, Uruk, G, Vardjan, N, Zorec, R, Mckenna, MC, (2024). Brain energy metabolism: A roadmap for future research Journal Of Neurochemistry 168, 910-954

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research. This article details current knowledge and major unknowns in brain energy metabolism and lays out a roadmap for future research.image

JTD Keywords: Acetate, Acetyl-coa, Aerobic glycolysis, Atp-citrate lyase, Extracellular glutamate concentration, Fatty-acid transport, Glucose-metabolism, Glut4, In-vivo, Insulin, Lipid droplet accumulation, Nicotinamide adenine-dinucleotide, Noradrenaline, Obese zucker rats, Rat cerebral-cortex


Eills, James, Picazo-Frutos, Roman, Bondar, Oksana, Cavallari, Eleonora, Carrera, Carla, Barker, Sylwia J, Utz, Marcel, Herrero-Gomez, Alba, Marco-Rius, Irene, Tayler, Michael C D, Aime, Silvio, Reineri, Francesca, Budker, Dmitry, Blanchard, John W, (2023). Enzymatic Reactions Observed with Zero- and Low-Field Nuclear Magnetic Resonance Analytical Chemistry 95, 17997-18005

We demonstrate that enzyme-catalyzed reactions can be observed in zero- and low-field NMR experiments by combining recent advances in parahydrogen-based hyperpolarization methods with state-of-the-art magnetometry. Specifically, we investigated two model biological processes: the conversion of fumarate into malate, which is used in vivo as a marker of cell necrosis, and the conversion of pyruvate into lactate, which is the most widely studied metabolic process in hyperpolarization-enhanced imaging. In addition to this, we constructed a microfluidic zero-field NMR setup to perform experiments on microliter-scale samples of [1-C-13]-fumarate in a lab-on-a-chip device. Zero- to ultralow-field (ZULF) NMR has two key advantages over high-field NMR: the signals can pass through conductive materials (e.g., metals), and line broadening from sample heterogeneity is negligible. To date, the use of ZULF NMR for process monitoring has been limited to studying hydrogenation reactions. In this work, we demonstrate this emerging analytical technique for more general reaction monitoring and compare zero- vs low-field detection.

JTD Keywords: Fumarates, Hydrogenation, Magnetic resonance imaging, Magnetic resonance spectroscopy, Nmr j-spectroscopy, Pyruvic acid


Fonte, M, Fontinha, D, Moita, D, Caño-Prades, O, Avalos-Padilla, Y, Fernàndez-Busquets, X, Prudencio, M, Gomes, P, Teixeira, C, (2023). New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial leads European Journal Of Medicinal Chemistry 258, 115575

A novel family of 4-aminoacridine derivatives was obtained by linking this heteroaromatic core to different trans-cinnamic acids. The 4-(N-cinnamoylbutyl)aminoacridines obtained exhibited in vitro activity in the low- or sub-micromolar range against (i) hepatic stages of Plasmodium berghei, (ii) erythrocytic forms of Plasmodium falciparum, and (iii) early and mature gametocytes of Plasmodium falciparum. The most active compound, having a meta-fluorocinnamoyl group linked to the acridine core, was 20- and 120-fold more potent, respectively, against the hepatic and gametocyte stages of Plasmodium infection than the reference drug, primaquine. Moreover, no cytotoxicity towards mammalian and red blood cells at the concentrations tested was observed for any of the compounds under investigation. These novel conjugates represent promising leads for the development of new multi-target antiplasmodials.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

JTD Keywords: agents, analogs, antimalarial, artemisinin, blood-stage, cinnamic acid, gametocyte, hybrid, liver-stage, malaria, multi-target, plasmodium-falciparum, primaquine, quinacrine, resistance, Acridine, Antimalarial, Blood-stage, Cinnamic acid, Cinnamic acid-derivatives, Gametocyte, Hybrid, Liver-stage, Multi-target


Colombi, S, Macor, LP, Ortiz-Membrado, L, Pérez-Amodio, S, Jiménez-Piqué, E, Engel, E, Pérez-Madrigal, MM, García-Torres, J, Alemán, C, (2023). Enzymatic Degradation of Polylactic Acid Fibers Supported on a Hydrogel for Sustained Release of Lactate Acs Applied Bio Materials 6, 3889-3901

The incorporation of exogenous lactate into cardiac tissues is a regenerative strategy that is rapidly gaining attention. In this work, two polymeric platforms were designed to achieve a sustained release of lactate, combining immediate and prolonged release profiles. Both platforms contained electrospun poly(lactic acid) (PLA) fibers and an alginate (Alg) hydrogel. In the first platform, named L/K(x)/Alg-PLA, lactate and proteinase K (x mg of enzyme per 1 g of PLA) were directly loaded into the Alg hydrogel, into which PLA fibers were assembled. In the second platform, L/Alg-K(x)/PLA, fibers were produced by electrospinning a proteinase K:PLA solution and, subsequently, assembled within the lactate-loaded hydrogel. After characterizing the chemical, morphological, and mechanical properties of the systems, as well as their cytotoxicity, the release profiles of the two platforms were determined considering different amounts of proteinase K (x = 5.2, 26, and 52 mg of proteinase K per 1 g of PLA), which is known to exhibit a broad cleavage activity. The profiles obtained using L/Alg-K(x)/PLA platforms with x = 26 and 52 were the closest to the criteria that must be met for cardiac tissue regeneration. Finally, the amount of lactate directly loaded in the Alg hydrogel for immediate release and the amount of protein in the electrospinning solution were adapted to achieve a constant lactate release of around 6 mM per day over 1 or 2 weeks. In the optimized bioplatform, in which 6 mM lactate was loaded in the hydrogel, the amount of fibers was increased by a factor of x3, the amount of enzyme was adjusted to 40 mg per 1 g of PLA, and a daily lactate release of 5.9 +/- 2.7 mM over a period of 11 days was achieved. Accordingly, the engineered device fully satisfied the characteristics and requirements for heart tissue regeneration.

JTD Keywords: biodegradable fibers, cardiac tissue regeneration, cell, drug-release, elastic-modulus, electrospinning, heart, nanoindentation, plasma treatment, proteinase, scaffold, stiffness, Alginate, Alginates, Biodegradable fibers, Cardiac tissue, Cardiac tissue regeneration, Cell, Delayed-action preparations, Drug-release, Elastic-modulus, Electrospinning, Endopeptidase k, Heart, Hydrogels, Lactic acid, Nanoindentation, Plasma treatment, Poly(lactide), Polyesters, Proteinase, Regeneration, Scaffold, Skeletal-muscle, Stiffness


Molina, BG, Ocón, G, Silva, FM, Iribarren, JI, Armelin, E, Alemán, C, (2023). Thermally-induced shape memory behavior of polylactic acid/ polycaprolactone blends European Polymer Journal 196, 112230

A study of the shape memory effect on extruded polylactic acid (PLA) and polycaprolactone (PCL) blends, which were transformed into films and movable components of articulated specimens by hot pressing and 3D printing, respectively, is presented. After characterizing their chemical structure by FTIR spectroscopy and their wetta-bility, the thermal properties and mechanical response of the blends were evaluated and compared with those of neat PLA and PCL. The blends exhibited very good interfacial adhesion between the phases, even though they are immiscible polymers. The thermoresponsive shape memory effects of neat PLA, neat PCL and PLA/PCL blends with different compositions (90/30, 70/30 and 50/50 w/w%) were evaluated considering three consecutive heating-cooling cycles. Comparison of the initial permanent state geometry with the geometries achieved after each heating-cooling cycle for both films and 3D printed specimens, evidenced that the 70/30 w/w% blend exhibited the best behavior. Thus, the blends obtained with such composition showed the maximum reversibility between the temporary and permanent states (i.e. highest shape recovery capability) and shape fixing of such two states.

JTD Keywords: 3d printing, Fibers, Films, Poly(lactic acid), Polycaprolactone, Polylactic acid, Polymer, Shape fixing, Shape-memory polymers, Unimolecular micelles


Dirisala, A, Li, JJ, Gonzalez-Carter, D, Wang, Z, (2023). Editorial: Delivery systems in biologics-based therapeutics Frontiers In Bioengineering And Biotechnology 11, 1274210

Eills, J, Picazo-Frutos, R, Burueva, DB, Kovtunova, LM, Azagra, M, Marco-Rius, I, Budker, D, Koptyug, IV, (2023). Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-13C]succinate Chemical Communications 59, 9509-9512

We show that catalyst-free aqueous solutions of hyperpolarized [1-13C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-13C]fumarate via PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/Al2O3 catalyst. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-13C]succinate as a hyperpolarized contrast agent.

JTD Keywords: acid, c-13, conversion, fumarate, in-vivo, metabolism, order, Induced polarization


Schmidt, AB, Eills, J, Dagys, L, Gierse, M, Bock, M, Lucas, S, Bock, M, Schwartz, I, Zaitsev, M, Chekmenev, EY, Knecht, S, (2023). Over 20% Carbon-13 Polarization of Perdeuterated Pyruvate Using Reversible Exchange with Parahydrogen and Spin-Lock Induced Crossing at 50 μT Journal Of Physical Chemistry Letters 14, 5305-5309

Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13C polarization (T1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.

JTD Keywords: hydrogen, nmr, Carbon isotopes, Carbon-13, Magnetic resonance imaging, Magnetic resonance spectroscopy, Pyruvic acid, Sabre


Placci, M, Giannotti, MI, Muro, S, (2023). Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders Advanced Drug Delivery Reviews 197, 114683

Lysosomes play a central role in cellular homeostasis and alterations in this compartment associate with many diseases. The most studied example is that of lysosomal storage disorders (LSDs), a group of 60 + maladies due to genetic mutations affecting lysosomal components, mostly enzymes. This leads to aberrant intracellular storage of macromolecules, altering normal cell function and causing multiorgan syndromes, often fatal within the first years of life. Several treatment modalities are available for a dozen LSDs, mostly consisting of enzyme replacement therapy (ERT) strategies. Yet, poor biodistribution to main targets such as the central nervous system, musculoskeletal tissue, and others, as well as generation of blocking antibodies and adverse effects hinder effective LSD treatment. Drug delivery systems are being studied to surmount these obstacles, including polymeric constructs and nanoparticles that consti-tute the focus of this article. We provide an overview of the formulations being tested, the diseases they aim to treat, and the results observed from respective in vitro and in vivo studies. We also discuss the advantages and disadvantages of these strategies, the remaining gaps of knowledge regarding their per-formance, and important items to consider for their clinical translation. Overall, polymeric nanocon-structs hold considerable promise to advance treatment for LSDs.(c) 2023 Elsevier B.V. All rights reserved.

JTD Keywords: cellular and animal models, enzyme replacement therapy, lysosomal storage disorders, nanoemulsions, nanoparticles, Beta-glucuronidase deficiency, Blood-brain-barrier, Cellular and animal models, Central-nervous-system, Drug delivery systems, Enzyme replacement therapy, Feline gm1 gangliosidosis, Human acid sphingomyelinase, Human alpha-galactosidase, Humans, Lysosomal storage diseases, Lysosomal storage disorders, Lysosomes, Mucopolysaccharidosis type-ii, Nanoemulsions, Nanoparticles, Neuronal ceroid-lipofuscinosis, Niemann-pick-disease, Pluripotent stem-cells, Polymer-based drug delivery systems, Polymers, Tissue distribution


Macor, LP, Colombi, S, Tamarit, JL, Engel, E, Pérez-Madrigal, MM, García-Torres, J, Alemán, C, (2023). Immediate-sustained lactate release using alginate hydrogel assembled to proteinase K/polymer electrospun fibers International Journal Of Biological Macromolecules 238, 124117

This work proposes a microfibers-hydrogel assembled composite as delivery vehicle able to combine into a single system both burst and prolonged release of lactate. The prolonged release of lactate has been achieved by electrospinning a mixture of polylactic acid and proteinase K (26.0 mg of proteinase K and 0.99 g of PLA dissolved in 6 mL of 2:1 chloroform:acetone in the optimal case), which is a protease that catalyzes the degradation of polylactic acid into lactate. The degradation of microfibers into lactate reflects that proteinase K preserves its enzymatic activity even after the electrospinning process because of the mild operational conditions used. Besides, burst release is obtained from the lactate-loaded alginate hydrogel. The successful assembly between the lactate-loaded hydrogel and the polylactic acid/proteinase K fibers has been favored by applying a low-pressure (0.3 mbar at 300 W) oxygen plasma treatment, which transforms hydrophobic fibers into hydrophilic while the enzymatic activity is still maintained. The composite displays both fast (< 24 h) and sustained (> 10 days) lactate release, and allows the modulation of the release by adjusting either the amount of loaded lactate or the amount of active enzyme.Copyright © 2023. Published by Elsevier B.V.

JTD Keywords: biodegradable fibers, proteases, regeneration, repair, Alginate, Alginates, Biodegradable fibers, Endopeptidase k, Hydrogels, Lactic acid, Myocardial-infarction, Polymers, Proteases


Borras, N, Sanchez-Sanz, A, Sans, J, Estrany, F, Perez-Madrigal, MM, Aleman, C, (2023). Flexible electroactive membranes for the electrochemical detection of dopamine European Polymer Journal 187, 111915

In addition of a key catecholamine neurotransmitter, dopamine is is the metabolite predominantly produced by specific types of tumors (e.g. paragangliomas and neuroblastomas), which cannot be diagnosed using conven-tional sensitive tests. Within this context, development of flexible electrochemical sensors to monitor dopamine levels in physiological fluids for the early diagnosis and control of diseases related to abnormal levels of such compound, is necessary. In this work, a flexible self-supported membrane, which acts directly as electrode, has been developed to detect dopamine. The membrane consists of three nanoperforated polylactic acid (PLA) layers, which provide flexibility and mechanical integrity, separated by two layers of an electroactive copolymer, which are obtained by electrochemical copolymerization of 3,4-ethylenedioxythiophene and aniline. The sensitivity and detection limit provided by the electroactive copolymer, which is accessible to dopamine molecules through the nanoperforations of the PLA outer layers, is 1.846 mu A/(cm2.mu M) and 1.7 mu M, respectively, in a urea-rich environments that mimics urine. These values allow us to propose the self-standing flexible electrodes devel-oped in this study for the detection of dopamine in patients affected by paragangliomas and neuroblastomas tumors, which typically present dopamine concentrations between 2 and 7 mu M.

JTD Keywords: 4-ethylenedioxythiophene), Conducting polymer, Electrochemical sensor, Electrodes, Hydrogels, Poly(3, Polyaniline, Polylactic acid, Selective detection, Sensors, Supercapacitors


Castrejón-Comas, V, Alemán, C, Pérez-Madrigal, MM, (2023). Multifunctional conductive hyaluronic acid hydrogels for wound care and skin regeneration Biomaterials Science 11, 2266-2276

Conductive and interactive hydrogels based on hyaluronic acid are engineered as wound dressings that enhance skin tissue regeneration either through electrical stimulation or by displaying multifunctional performance and, ultimately, interactivity.

JTD Keywords: antibacterial, fields, Anti-bacterial agents, Bacterial infections, Humans, Hyaluronic acid, Hydrogels, Injectable hydrogels, Skin, Wound healing


Chausse, V, Iglesias, C, Bou-Petit, E, Ginebra, MP, Pegueroles, M, (2023). Chemical vs thermal accelerated hydrolytic degradation of 3D-printed PLLA/PLCL bioresorbable stents: Characterization and influence of sterilization Polymer Testing 117, 107817

Bioresorbable stents (BRS) are designed to provide initial sufficient mechanical support to prevent vessel recoil while being degraded until their complete resorption. Therefore, degradation rate of BRS plays a crucial role in successful stent performance. This work presents a complete study on the degradation of poly-llactic acid (PLLA) and poly(lactic-co-epsilon-caprolactone) (PLCL) stents fabricated by solvent-cast direct-writing (SC-DW) through two different accelerated assays: alkaline medium at 37 degrees C for 10 days and PBS at 50 degrees C for 4 months. On retrieval, degraded stents were characterized in terms of mass loss, molecular weight (Mw), thermal and mechanical properties. The results showed that under alkaline conditions, stents underwent surface erosion, whereas stents immersed in PBS at 50 degrees C experienced bulk degradation. M-n decrease was accurately described by the autocatalyzed kinetic model, with PLCL showing a degradation rate 1.5 times higher than PLLA. Additionally, stents were subjected to gamma-irradiation and ethylene oxide (EtO) sterilization. Whereas EtOsterilized stents remained structurally unaltered, gamma-irradiated stents presented severe deterioration as a result of extensive chain scission.

JTD Keywords: Acid, Behavior, Bioresorbable stents, Copolymer, Hydrolytic degradation, In-vitro degradation, Mechanical-properties, Molecular-weight, Poly(l-lactide), Poly-l-lactic acid, Poly-l-lactide, Scaffolds, Solvent-cast direct-writing, Sterilization


Guallar-Garrido, S, Campo-Perez, V, Perez-Trujillo, M, Cabrera, C, Senserrich, J, Sanchez-Chardi, A, Rabanal, RM, Gomez-Mora, E, Noguera-Ortega, E, Luquin, M, Julian, E, (2022). Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-gamma/IL-17 release in bladder cancer treatment Oncoimmunology 11, 2051845

The mechanism of action of intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic Mycobacterium brumae were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model. Our data reveal that each mycobacterium requires specific culture conditions to induce an effective antitumor response. since higher survival rates of tumor-bearing mice were achieved using M. brumae-A60 and BCG-G15 than the rest of the treatments. M. brumae-A60 was the most efficacious among all tested treatments in terms of mouse survival, cytotoxic activity of splenocytes against tumor cells, higher systemic production of IL-17 and IFN-gamma, and bladder infiltration of selected immune cells such as ILCs and CD4(TEM). BCG-G15 triggered an antitumor activity based on a massive infiltration of immune cells, mainly CD3(+) (CD4(+) and CD8(+)) T cells, together with high systemic IFN-gamma release. Finally, a reduced variety of lipids was strikingly observed in the outermost layer of M. brumae-A60 and BCG-G15 compared to the rest of the cultures, suggesting an influence on the antitumor immune response triggered. These findings contribute to understand how mycobacteria create an adequate niche to help the host subvert immunosuppressive tumor actions.

JTD Keywords: bcg, innate immune response, innate-lymphoid cells, lipid, non-muscle invasive, Bcg, Calmette-guerin bcg, Glycerol, Identification, Immune-response, Innate immune response, Innate-lymphoid cells, Lipid, Lipids, Mycolic acids, Neutral-red, Non-muscle invasive, Phenolic glycolipids, Tuberculosis, Tumor microenvironment, Virulence


Bertran, O, Martí, D, Torras, J, Turon, P, Alemán, C, (2022). Computer simulations on oxidative stress-induced reactions in SARS-CoV-2 spike glycoprotein: a multi-scale approach Molecular Diversity 26, 3143-3155

Abstract Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in a misbalance of antioxidant and pro-oxidants species, is the common denominator of diseases considered as a risk factor for SARS-CoV-2 lethality. Indeed, reactive oxygen species caused by oxidative stress have been related to many virus pathogenicity. In this work, simulations have been performed on the receptor binding domain of SARS-CoV-2 spike glycoprotein to study what residues are more susceptible to be attacked by ·OH, which is one of the most reactive radicals associated to oxidative stress. The results indicate that isoleucine (ILE) probably plays a crucial role in modification processes driven by radicals. Accordingly, QM/MM-MD simulations have been conducted to study both the ·OH-mediated hydrogen abstraction of ILE residues and the induced modification of the resulting ILE radical through hydroxylation or nitrosylation reactions. All in all, in silico studies show the importance of the chemical environment triggered by oxidative stress on the modifications of the virus, which is expected to help for foreseeing the identification or development of antioxidants as therapeutic drugs. Graphic abstract

JTD Keywords: atom abstraction, damage, density functionals, hydrogen abstraction, isoleucine, molecular dynamics, pathogenesis, protein, reactive oxygen species, receptor binding domain, residues, spike protein, Amino-acids, Hydrogen abstraction, Isoleucine, Molecular dynamics, Reactive oxygen species, Receptor binding domain, Spike protein


Fischer, NG, Aparicio, C, (2022). Junctional epithelium and hemidesmosomes: Tape and rivets for solving the “percutaneous device dilemma” in dental and other permanent implants Bioactive Materials 18, 178-198

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the “device”/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant – as a model percutaneous device – placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists. © 2022 The Authors

JTD Keywords: amino-acid-sequence, bioinspired surfaces, cell-secreted protein, growth-factor receptor, hemidesmosome, integrin beta-4 subunit, junctional epithelium, keratinocyte-derived chemokine, laminin-binding integrins, marginal bone loss, percutaneous device, percutaneous implant, pressure wound therapy, soft-tissue integration, Bioinspired surfaces, Bullous-pemphigoid antigen, Hemidesmosome, Junctional epithelium, Percutaneous device, Percutaneous implant


Molina, BG, Vasani, RB, Jarvis, KL, Armelin, E, Voelcker, NH, Aleman, C, (2022). Dual pH- and electro-responsive antibiotic-loaded polymeric platforms for effective bacterial detection and elimination Reactive & Functional Polymers 181, 105434

We describe a multi-tasking flexible system that is able to release a wide spectrum antibiotic (levofloxacin, LVX) under electrostimulation and act as a pH sensor for detecting bacterial infections. Combining anodic polymer-ization with plasma polymerization processes we engineered dual pH-and electro-responsive polymeric systems. Particularly, the manufactured devices consisted on a layer of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHEDOT) loaded with the LVX antibiotic and coated with a plasma polymer layer of poly(acrylic acid) (PAA). The PHEDOT acted as conductive and electro-responsive agent, while the PAA provided pH responsiveness, changing from a compact globular conformation in acid environments to an expanded open coil conformation in alkaline environments. The assembly between the PHEDOT layer and the PAA coating affected the electro-chemical response of the former, becoming dependent on the pH detected by the latter. The conformational change experienced by the PAA layer as a function of the pH and the redox properties of PHEDOT were leveraged for the electrochemical detection of bacteria growth and for regulating the release of the LVX antibiotic, respectively. The effectiveness of the system as a stimulus-responsive antibiotic carrier and pH sensor was also investigated on strains of Escherichia coli and Streptococcus salivarius.

JTD Keywords: Conducting polymer, Delivery, Drug delivery, Electrostimulation, Levofloxacin, Ph sensor, Plasma, Poly(acrylic acid), Selective detection


García-Torres, J, Colombi, S, Macor, LP, Alemán, C, (2022). Multitasking smart hydrogels based on the combination of alginate and poly(3,4-ethylenedioxythiophene) properties: A review International Journal Of Biological Macromolecules 219, 312-332

Poly(3,4-ethylenedioxythiophene) (PEDOT), a very stable and biocompatible conducting polymer, and alginate (Alg), a natural water-soluble polysaccharide mainly found in the cell wall of various species of brown algae, exhibit very different but at the same complementary properties. In the last few years, the remarkable capacity of Alg to form hydrogels and the electro-responsive properties of PEDOT have been combined to form not only layered composites (PEDOT-Alg) but also interpenetrated multi-responsive PEDOT/Alg hydrogels. These materials have been found to display outstanding properties, such as electrical conductivity, piezoelectricity, biocompatibility, self-healing and re-usability properties, pH and thermoelectric responsiveness, among others. Consequently, a wide number of applications are being proposed for PEDOT-Alg composites and, especially, PEDOT/Alg hydrogels, which should be considered as a new kind of hybrid material because of the very different chemical nature of the two polymeric components. This review summarizes the applications of PEDOT-Alg and PEDOT/Alg in tissue interfaces and regeneration, drug delivery, sensors, microfluidics, energy storage and evaporators for desalination. Special attention has been given to the discussion of multi-tasking applications, while the new challenges to be tackled based on aspects not yet considered in either of the two polymers have also been highlighted.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

JTD Keywords: aerogels, composite, conducting polymer, conducting polymers, electrodes, pedotpss, ph, platform, release, scaffold, semi-interpenetrated hydrogels, Alginates, Alginic acid, Bridged bicyclo compounds, heterocyclic, Conducting polymer, Drug-delivery, Hydrogels, Poly(3,4-ethylene dioxythiophene), Polymers, Polysaccharides, Semi-interpenetrated hydrogels, Water


Pala, M, El Khannaji, H, Garay-Sarmiento, M, Ronda, JC, Cadiz, V, Galia, M, Percec, V, Rodriguez-Emmenegger, C, Lligadas, G, (2022). A green solvent-to-polymer upgrading approach to water-soluble LCST poly(N-substituted lactamide acrylate)s Green Chemistry 24, 8314-8323

We report a green solvent-to-polymer upgrading transformation of chemicals of the lactic acid portfolio into water-soluble lower critical solution temperature (LCST)-type acrylic polymers. Aqueous Cu(0)-mediated living radical polymerization (SET-LRP) was utilized for the rapid synthesis of N-substituted lactamide-type homo and random acrylic copolymers under mild conditions. A particularly unique aspect of this work is that the water-soluble monomers and the SET-LRP initiator used to produce the corresponding polymers were synthesized from biorenewable and non-toxic solvents, namely natural ethyl lactate and BASF's Agnique (R) AMD 3L (N,N-dimethyl lactamide, DML). The pre-disproportionation of Cu(I) Br in the presence of tris[2-(dimethylamino)ethyl]amine (Me6TREN) in water generated nascent Cu(0) and Cu(II) complexes that facilitated the fast polymerization of N-tetrahydrofurfuryl lactamide and N,N-dimethyl lactamide acrylate monomers (THFLA and DMLA, respectively) up to near-quantitative conversion with excellent control over molecular weight (5000 < M-n < 83 000) and dispersity (1.05 < D < 1.16). Interestingly, poly(THFLA) showed a degree of polymerization and concentration dependent LCST behavior, which can be fine-tuned (T-cp = 12-62 degrees C) through random copolymerization with the more hydrophilic DMLA monomer. Finally, covalent cross-linking of these polymers resulted in a new family of thermo-responsive hydrogels with excellent biocompatibility and tunable swelling and LCST transition. These illustrate the versatility of these neoteric green polymers in the preparation of smart and biocompatible soft materials.

JTD Keywords: Acid, Ethyl lactate, Living radical polymerization, Monomers, Pnipam, Reductive amination, Ruthenium nanoparticles, Set-lrp, Single, Thermoresponsive polymers


Bartova, S, Madrid-Gambin, F, Fernandez, L, Carayol, J, Meugnier, E, Segrestin, B, Delage, P, Vionnet, N, Boizot, A, Laville, M, Vidal, H, Marco, S, Hager, J, Moco, S, (2022). Grape polyphenols decrease circulating branched chain amino acids in overfed adults Front Nutr 9, 998044

Introduction and aimsDietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials.MethodsBlood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 atResultsChanges in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study.ConclusionAdministration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.

JTD Keywords: branched chain amino acids, grape polyphenols, human trials, metabolism, metabolomics, nmr, obesity, Branched chain amino acids, Grape polyphenols, Human trials, Metabolism, Metabolomics, Nmr, Obesity, Overfeeding


Sans, J, Arnau, M, Sanz, V, Turon, P, Aleman, C, (2022). Fine-tuning of polarized hydroxyapatite for the catalytic conversion of dinitrogen to ammonium under mild conditions Chemical Engineering Journal 446, 137440

Polarized hydroxyapatite (p-HAp), a calcium phosphate catalyst obtained at high temperature under intense electric field, has been used for the synthesis of ammonium starting from N2 and liquid water at low pressure (<6 bar) and temperatures below 120 C. The success of the nitrogen fixation process has been demonstrated by isotope labelling experiments using 15N2. Considering the optimal reaction conditions for the production of ammonium, the yield is as high as 154.6 +/- 25.8 mu mol/g of catalyst. The proposed synthesis exhibits three important advantages for its utilization in green chemistry environmental processes related to the recycling of polluted air. These are: i) the catalysts converts CO2 into valuable chemical products in addition of transforming N2 in ammonium; ii) the final energy balance is very favorable since no external electrical field is necessary to promote nitrogen and carbon fixation reactions; and iii) products are easily transferred to water favoring their extraction and avoiding the saturation of the catalyst.

JTD Keywords: Adsorbed nitrogen, Air pollution, Amino-acids, Electrophotosynthesis, Environmental process, Facile synthesis, Fixation, Functionalization, Hydroxyapatite, Nitride, Nitrogen reduction, Polarized catalyst


De Lama-Odría, MD, Del Valle, LJ, Puiggalí, J, (2022). Hydroxyapatite Biobased Materials for Treatment and Diagnosis of Cancer International Journal Of Molecular Sciences 23, 11352

Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with decreasing side effects and a better understanding of the behavior of neoplastic cells during invasion and metastasis. Specifically, drug delivery systems (DDS) based on the use of hydroxyapatite nanoparticles (HAp NPs) are gaining attention and merit a comprehensive review focused on their potential applications. These are derived from the intrinsic properties of HAp (e.g., biocompatibility and biodegradability), together with the easy functionalization and easy control of porosity, crystallinity and morphology of HAp NPs. The capacity to tailor the properties of DLS based on HAp NPs has well-recognized advantages for the control of both drug loading and release. Furthermore, the functionalization of NPs allows a targeted uptake in tumoral cells while their rapid elimination by the reticuloendothelial system (RES) can be avoided. Advances in HAp NPs involve not only their use as drug nanocarriers but also their employment as nanosystems for magnetic hyperthermia therapy, gene delivery systems, adjuvants for cancer immunotherapy and nanoparticles for cell imaging.

JTD Keywords: antitumoral, cancer, cell imaging, controlled-release, drug-carrier, efficient drug-delivery, fatty-acid-metabolism, fe3o4 nanoparticles, gene delivery, hydroxyapatite, hyperthermia, immunotherapy, in-vitro, magnetic hydroxyapatite, nano-hydroxyapatite, protein adsorption, tumor-growth, Calcium-phosphate nanoparticles, Cancer, Immunotherapy


Solomon, M, Loeck, M, Silva-Abreu, M, Moscoso, R, Bautista, R, Vigo, M, Muro, S, (2022). Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases Journal Of Controlled Release 349, 1031-1044

Treatment of neurological lysosomal storage disorders (LSDs) are limited because of impermeability of the blood-brain barrier (BBB) to macromolecules. Nanoformulations targeting BBB transcytosis are being explored, but the status of these routes in LSDs is unknown. We studied nanocarriers (NCs) targeted to the transferrin receptor (TfR), ganglioside GM1 or ICAM1, associated to the clathrin, caveolar or cell adhesion molecule (CAM) routes, respectively. We used brain endothelial cells and mouse models of acid sphingomyelinase-deficient Niemann Pick disease (NPD), and postmortem LSD patients' brains, all compared to respective controls. NC transcytosis across brain endothelial cells and brain distribution in mice were affected, yet through different mechanisms. Reduced TfR and clathrin expression were found, along with decreased transcytosis in cells and mouse brain distribution. Caveolin-1 expression and GM1 transcytosis were also reduced, yet increased GM1 levels seemed to compensate, providing similar NC brain distribution in NPD vs. control mice. A tendency to lower NHE-1 levels was seen, but highly increased ICAM1 expression in cells and human brains correlated with increased transcytosis and brain distribution in mice. Thus, transcytosis-related alterations in NPD and likely other LSDs may impact therapeutic access to the brain, illustrating the need for these mechanistic studies.Copyright © 2022 Elsevier B.V. All rights reserved.

JTD Keywords: acid sphingomyelinase, antibody-affinity, blood -brain barrier, drug-delivery, icam-1-targeted nanocarriers, in-vivo, mediated endocytosis, model, neurological diseases, niemann-pick, targeted nanocarriers, trafficking, transcytosis pathways, Animals, Blood-brain barrier, Brain, Caveolin 1, Central-nervous-system, Clathrin, Endothelial cells, G(m1) ganglioside, Humans, Lysosomal storage diseases, Lysosomal storage disorders, Mice, Neurological diseases, Receptors, transferrin, Sphingomyelin phosphodiesterase, Targeted nanocarriers, Transcytosis, Transcytosis pathways


Perez-Madrigala, MM, Gilb, AM, Casanovas, J, Jimenez, AI, Macor, LP, Aleman, C, (2022). Self-assembly pathways in a triphenylalanine peptide capped with aromatic groups Colloids And Surfaces B-Biointerfaces 216, 112522

Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphe-nylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N-and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylme-thyloxycarbonyl and benzyl ester end-capping groups at the N-and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in beta-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm beta-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the mediu m on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addi-tion, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of pi-pi stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which de-termines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.

JTD Keywords: aromatic interactions, beta-sheet, hierarchical structures, phenylalanine homopeptides, supramolecular structures, Amino-acids, Aromatic interactions, Beta-sheet, Dipeptides, Diphenylalanine, Fmoc, Hierarchical struc tures, Hierarchical structures, Hydrogels, Peptides, Phenylalanine, Phenylalanine homopeptides, Solvent, Solvents, Spectroscopy, Supramolecular structures, Triphenylalanine


Roki, N, Solomon, M, Bowers, J, Getts, L, Getts, RC, Muro, S, (2022). Tuning Design Parameters of ICAM-1-Targeted 3DNA Nanocarriers to Optimize Pulmonary Targeting Depending on Drug Type Pharmaceutics 14, 1496

3DNA holds promise as a carrier for drugs that can be intercalated into its core or linked to surface arms. Coupling 3DNA to an antibody targeting intercellular adhesion molecule 1 (ICAM-1) results in high lung-specific biodistributions in vivo. While the role of individual parameters on ICAM-1 targeting has been studied for other nanocarriers, it has never been examined for 3DNA or in a manner capable of revealing the hierarchic interplay among said parameters. In this study, we used 2-layer vs. 4-layer anti-ICAM 3DNA and radiotracing to examine biodistribution in mice. We found that, below saturating conditions and within the ranges tested, the density of targeting antibodies on 3DNA is the most relevant parameter driving lung targeting over liver clearance, compared to the number of antibodies per carrier, total antibody dose, 3DNA dose, 3DNA size, or the administered concentration, which influenced the dose in organs but not the lung specific-over-liver clearance ratio. Data predicts that lung-specific delivery of intercalating (core loaded) drugs can be tuned using this biodistribution pattern, while that of arm-linked (surface loaded) drugs requires a careful parametric balance because increasing anti-ICAM density reduces the number of 3DNA arms available for drug loading.

JTD Keywords: 3dna nanocarrier, acid sphingomyelinase, antibody, carrier design parameters, carriers, dna nanostructures, doxorubicin, drug type, icam-1, inflammation, lung targeting, multiparametric hierarchy, nanoparticles, size, 3dna nanocarrier, Intracellular delivery, Multiparametric hierarchy


Clua-Ferre, L, De Chiara, F, Rodriguez-Comas, J, Comelles, J, Martinez, E, Godeau, AL, Garcia-Alaman, A, Gasa, R, Ramon-Azcon, J, (2022). Collagen-Tannic Acid Spheroids for beta-Cell Encapsulation Fabricated Using a 3D Bioprinter Advanced Materials Technologies 7, 2101696

Type 1 Diabetes results from autoimmune response elicited against β-cell antigens. Nowadays, insulin injections remain the leading therapeutic option. However, injection treatment fails to emulate the highly dynamic insulin release that β-cells provide. 3D cell-laden microspheres have been proposed during the last years as a major platform for bioengineering insulin-secreting constructs for tissue graft implantation and a model for in vitro drug screening platforms. Current microsphere fabrication technologies have several drawbacks: the need for an oil phase containing surfactants, diameter inconsistency of the microspheres, and high time-consuming processes. These technologies have widely used alginate for its rapid gelation, high processability, and low cost. However, its low biocompatible properties do not provide effective cell attachment. This study proposes a high-throughput methodology using a 3D bioprinter that employs an ECM-like microenvironment for effective cell-laden microsphere production to overcome these limitations. Crosslinking the resulting microspheres with tannic acid prevents collagenase degradation and enhances spherical structural consistency while allowing the diffusion of nutrients and oxygen. The approach allows customization of microsphere diameter with extremely low variability. In conclusion, a novel bio-printing procedure is developed to fabricate large amounts of reproducible microspheres capable of secreting insulin in response to extracellular glucose stimuli.© 2022 The Authors. Advanced Materials Technologies published by Wiley‐VCH GmbH.

JTD Keywords: 3d bioprinter, beta-cell, biomaterial, collagen, encapsulation, mechanics, microspheres, survival, 3d bioprinter, ?-cell, Advanced material technologies, Biocompatibility, Cell encapsulations, Cells, Collagen, Cross-linking, Cytology, Drug delivery, Encapsulation, Fabrication, Flavonoids, Gelation, In-vitro, Insulin injections, Insulin release, Microspheres, Tannic acid, Tannins, Throughput, Tissue grafts, Type 1 diabetes, Β‐cell


Sans, J, Arnau, M, Roa, JJ, Turon, P, Alernan, C, (2022). Tailorable Nanoporous Hydroxyapatite Scaffolds for Electrothermal Catalysis Acs Applied Nano Materials 5, 8526-8536

Polarized hydroxyapatite (HAp) scaffolds with customized architecture at the nanoscale have been presented as a green alternative to conventional catalysts used for carbon and dinitrogen fixation. HAp printable inks with controlled nanoporosity and rheological properties have been successfully achieved by incorporating Pluronic hydrogel. Nanoporous scaffolds with good mechanical properties, as demonstrated by means of the nanoindentation technique, have been obtained by a sintering treatment and the posterior thermally induced polarization process. Their catalytic activity has been evaluated by considering three different key reactions (all in the presence of liquid water): (1) the synthesis of amino acids from gas mixtures of N-2, CO2, and CH4; (2) the production of ethanol from gas mixtures of CO2 and CH4; and (3) the synthesis of ammonia from N-2 gas. Comparison of the yields obtained by using nanoporous and nonporous (conventional) polarized HAp catalysts shows that both the nanoporosity and water absorption capacity of the former represent a drawback when the catalytic reaction requires auxiliary coating layers, as for example for the production of amino acids. This is because the surface nanopores achieved by incorporating Pluronic hydrogel are completely hindered by such auxiliary coating layers. On the contrary, the catalytic activity improves drastically for reactions in which the HAp-based scaffolds with enhanced nanoporosity are used as catalysts. More specifically, the carbon fixation from CO2 and CH4 to yield ethanol improves by more than 3000% when compared with nonporous HAp catalyst. Similarly, the synthesis of ammonia by dinitrogen fixation increases by more than 2000%. Therefore, HAp catalysts based on nanoporous scaffolds exhibit an extraordinary potential for scalability and industrial utilization for many chemical reactions, enabling a feasible green chemistry alternative to catalysts based on heavy metals.

JTD Keywords: Amino acids, Amino-acids, Ammonium production, Bone, Carbon fixation, Composites, Constitutive phases, Decarbonization, Dinitrogen, Ditrogen fixation, Elastic-modulus, Electrophotosynthesis, Ethanol production, Hardness, Indentation, Nanoindentation, Pluronic hydrogel, Polarized hydroxyapatite


Enshaei, H, Molina, BG, Puiggali-Jou, A, Saperas, N, Aleman, C, (2022). Polypeptide hydrogel loaded with conducting polymer nanoparticles as electroresponsive delivery system of small hydrophobic drugs European Polymer Journal 173, 111199

A hydrogel/nanoparticle-loaded system for the controlled delivery of small hydrophobic drugs has been prepared using poly(gamma-glutamic acid) (PGGA), a naturally occurring biopolymer made of glutamic acid units connected by amide linkages between alpha-amino and gamma-carboxylic acid groups, and poly(3,4-ethylenedioxythiophene) (PEDOT), a very stable conducting polymer with excellent electrochemical response. Specifically, curcumin (CUR)-loaded PEDOT nanoparticles (PEDOT/CUR) were incorporated to the PGGA hydrogel during the crosslinking reaction. After chemical, morphological and electrochemical characterization, the release profiles of PEDOT/CUR and PGGA/PEDOT/CUR system have been compared in absence and presence of electrical stimuli, which consisted on the application of a voltage of -0.5 V for 15 min every 24 h. Results show that the release is higher for electrically stimulated systems by more than twice, even though due to its hydrophobicity and poor solubility in water the release was relatively slow in both cases. This feature could be advantageous when the therapeutic treatment requires slow, controlled and sustained CUR release.

JTD Keywords: 4-ethylenedioxythiophene), Acid, Controlled-release, Curcumi n, Curcumin, Electrostimulated release, Nanocarriers, Pedotpss, Poly( ?-glutamic acid), Poly(3


Sans, J, Arnau, M, Turon, P, Alemán, C, (2022). Permanently polarized hydroxyapatite, an outstanding catalytic material for carbon and nitrogen fixation Materials Horizons 9, 1566-1576

Permanently polarized hydroxyapatite is a new material with electrical enhanced properties. This review discusses the advances in this material in terms of structure, properties and catalytic activity of green processes.

JTD Keywords: ammonia, bone, copper hydroxyapatite, electrophotosynthesis, nanoparticles, oxidation, phase-transition, reduction, Amino-acids


Garrido-Charles, A, Huet, A, Matera, C, Thirumalai, A, Hernando, J, Llebaria, A, Moser, T, Gorostiza, P, (2022). Fast Photoswitchable Molecular Prosthetics Control Neuronal Activity in the Cochlea Journal Of The American Chemical Society 144, 9229-9239

Artificial control of neuronal activity enables the study of neural circuits and restoration of neural functions. Direct, rapid, and sustained photocontrol of intact neurons could overcome the limitations of established electrical stimulation such as poor selectivity. We have developed fast photoswitchable ligands of glutamate receptors (GluRs) to enable neuronal control in the auditory system. The new photoswitchable ligands induced photocurrents in untransfected neurons upon covalently tethering to endogenous GluRs and activating them reversibly with visible light pulses of a few milliseconds. As a proof of concept of these molecular prostheses, we applied them to the ultrafast synapses of auditory neurons of the cochlea that encode sound and provide auditory input to the brain. This drug-based method afforded the optical stimulation of auditory neurons of adult gerbils at hundreds of hertz without genetic manipulation that would be required for their optogenetic control. This indicates that the new photoswitchable ligands are also applicable to the spatiotemporal control of fast spiking interneurons in the brain.

JTD Keywords: Acid, Azobenzene, Glutamate-receptor, Ion channels, Mechanisms, Nerve, Optical switches, Release, Stimulation


Casanellas, I, Lagunas, A, Vida, Y, Perez-Inestrosa, E, Rodriguez-Pereira, C, Magalhaes, J, Andrades, JA, Becerra, J, Samitier, J, (2022). Nanoscale ligand density modulates gap junction intercellular communication of cell condensates during chondrogenesis Nanomedicine 17, 775-791

Aim: To unveil the influence of cell-matrix adhesions in the establishment of gap junction intercellular communication (GJIC) during cell condensation in chondrogenesis. Materials & methods: Previously developed nanopatterns of the cell adhesive ligand arginine-glycine-aspartic acid were used as cell culture substrates to control cell adhesion at the nanoscale. In vitro chondrogenesis of mesenchymal stem cells was conducted on the nanopatterns. Cohesion and GJIC were evaluated in cell condensates. Results: Mechanical stability and GJIC are enhanced by a nanopattern configuration in which 90% of the surface area presents adhesion sites separated less than 70 nm, thus providing an onset for cell signaling. Conclusion: Cell-matrix adhesions regulate GJIC of mesenchymal cell condensates during in vitro chondrogenesis from a threshold configuration at the nanoscale.

JTD Keywords: arginine-glycine-aspartic acid, arginine–glycine–aspartic acid, cell adhesion, condensation, dendrimer-based nanopatterning, gap junction intercellular communication, Actin, Adhesion, Arginine-glycine-aspartic acid, Cell adhesion, Collagen, Condensation, Connexin-43, Dendrimer-based nanopatterning, Dynamics, Extracellular-matrix, Fibronectin, Gap junction intercellular communication, Mesenchymal stem cells, Permeability, Phenotype, Vinculin


Muntimadugu, E, Silva-Abreu, M, Vives, G, Loeck, M, Pham, V, Del Moral, M, Solomon, M, Muro, S, (2022). Comparison between Nanoparticle Encapsulation and Surface Loading for Lysosomal Enzyme Replacement Therapy International Journal Of Molecular Sciences 23, 4034

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A–B Niemann–Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.

JTD Keywords: active enzymes, encapsulation, enhanced delivery, enzyme therapeutics, formulation parameters, icam-1 targeting, icam-1-targeted nanocarriers, in vivo biodistribution, in-vitro, lysosomal delivery, model, oral delivery, plga nanoparticles, poly(lactic-co-glycolic acid) nanoparticles, protein therapeutics, surface loading, Acid sphingomyelinase, Animals, Encapsulation, Enzyme replacement therapy, Enzyme therapeutics, Icam-1 targeting, In vivo biodistribution, Lysosomal delivery, Lysosomes, Mice, Nanoparticles, Poly(lactic-co-glycolic acid) nanoparticles, Polymers, Surface loading, Surface-active agents


Sans, J, Arnau, M, Sanz, V, Turon, P, Alemán, C, (2022). Hydroxyapatite-based biphasic catalysts with plasticity properties and its potential in carbon dioxide fixation Chemical Engineering Journal 433, 133512

The design of catalysts with controlled selectivity at will, also known as catalytic plasticity, is a very attractive approach for the recycling of carbon dioxide (CO2). In this work, we study how catalytically active hydroxyapatite (HAp) and brushite (Bru) interact synergistically, allowing the production of formic acid or acetic acid depending on the HAp/Bru ratio in the catalyst. Raman, wide angle X-ray scattering, X-ray photoelectron spectroscopy, scanning electron microscopy and electrochemical impedance spectroscopy studies, combined with an exhaustive revision of the crystalline structure of the catalyst at the atomic level, allowed to discern how the Bru phase can be generated and stabilized at high temperatures. Results clearly indicate that the presence of OH– groups to maintain the crystalline structural integrity in conjunction with Ca2+ ions less bonded to the lattice fixate carbon into C1, C2 and C3 molecules from CO2 and allow the evolution from formic to acetic acid and acetone. In this way, the plasticity of the HAp-Bru system is demonstrated, representing a promising green alternative to the conventional metal-based electrocatalysts used for CO2 fixation. Thus, the fact that no electric voltage is necessary for the CO2 reduction has a very favorable impact in the final energetic net balance of the carbon fixation reaction. © 2021

JTD Keywords:

ethanol production & nbsp, brushite, co2 reduction, conversion, electrocatalytic reduction, electrode, formate, heterogeneous catalysis & nbsp, hydrogen evolution, insights, monetite, polarized hydroxyapatite,

, Acetic acid, Acetone, Biphasic catalyst, Brushite, Calcium phosphate, Carbon dioxide, Carbon dioxide fixation, Catalysis, Catalyst selectivity, Co 2 reduction, Co2 reduction, Electrocatalysts, Electrochemical impedance spectroscopy, Electrochemical reduction, Electrochemical-impedance spectroscopies, Ethanol production, Formic acid, Heterogeneous catalysis, Hydroxyapatite, Ph, Polarized hydroxyapatite, Property, Reduction, Scanning electron microscopy, Temperature programmed desorption, Wide angle x-ray scattering, X ray photoelectron spectroscopy, X ray scattering, ]+ catalyst


Oliveras, T, Lazaro, I, Rueda, F, Cediel, G, Bhatt, DL, Fito, M, Madrid-Gambin, F, Pozo, OJ, Harris, WS, Garcia-Garcia, C, Sala-Vila, A, Bayes-Genis, A, (2022). Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation Scientific Reports 12, 4377

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

JTD Keywords: Arrhythmias, Fish-oil, Omega-3-fatty-acids, Sudden cardiac death


Bonilla-Pons, SA, Nakagawa, S, Bahima, EG, Fernández-Blanco, A, Pesaresi, M, D'Antin, JC, Sebastian-Perez, R, Greco, D, Domínguez-Sala, E, Gómez-Riera, R, Compte, RIB, Dierssen, M, Pulido, NM, Cosma, MP, (2022). Müller glia fused with adult stem cells undergo neural differentiation in human retinal models Ebiomedicine 77, 103914

Visual impairments are a critical medical hurdle to be addressed in modern society. Müller glia (MG) have regenerative potential in the retina in lower vertebrates, but not in mammals. However, in mice, in vivo cell fusion between MG and adult stem cells forms hybrids that can partially regenerate ablated neurons.We used organotypic cultures of human retina and preparations of dissociated cells to test the hypothesis that cell fusion between human MG and adult stem cells can induce neuronal regeneration in human systems. Moreover, we established a microinjection system for transplanting human retinal organoids to demonstrate hybrid differentiation.We first found that cell fusion occurs between MG and adult stem cells, in organotypic cultures of human retina as well as in cell cultures. Next, we showed that the resulting hybrids can differentiate and acquire a proto-neural electrophysiology profile when the Wnt/beta-catenin pathway is activated in the adult stem cells prior fusion. Finally, we demonstrated the engraftment and differentiation of these hybrids into human retinal organoids.We show fusion between human MG and adult stem cells, and demonstrate that the resulting hybrid cells can differentiate towards neural fate in human model systems. Our results suggest that cell fusion-mediated therapy is a potential regenerative approach for treating human retinal dystrophies.This work was supported by La Caixa Health (HR17-00231), Velux Stiftung (976a) and the Ministerio de Ciencia e Innovación, (BFU2017-86760-P) (AEI/FEDER, UE), AGAUR (2017 SGR 689, 2017 SGR 926).Published by Elsevier B.V.

JTD Keywords: cell fusion, expression, fusion, ganglion-cells, in-vitro, mouse, müller glia, neural differentiation, organoids, regeneration, retina regeneration, stem cells, stromal cells, transplantation, 4',6 diamidino 2 phenylindole, 5' nucleotidase, Agarose, Alcohol, Arpe-19 cell line, Article, Beta catenin, Beta tubulin, Bone-marrow-cells, Bromophenol blue, Buffer, Calcium cell level, Calcium phosphate, Calretinin, Canonical wnt signaling, Cd34 antigen, Cell culture, Cell fusion, Cell viability, Coculture, Complementary dna, Confocal microscopy, Cornea transplantation, Cryopreservation, Cryoprotection, Crystal structure, Current clamp technique, Dimethyl sulfoxide, Dodecyl sulfate sodium, Edetic acid, Electrophysiology, Endoglin, Fetal bovine serum, Fibroblast growth factor 2, Flow cytometry, Fluorescence activated cell sorting, Fluorescence intensity, Glyceraldehyde 3 phosphate dehydrogenase, Glycerol, Glycine, Hoe 33342, Immunofluorescence, Immunohistochemistry, Incubation time, Interleukin 1beta, Lentivirus vector, Matrigel, Mercaptoethanol, Microinjection, Mueller cell, Müller glia, N methyl dextro aspartic acid, Nerve cell differentiation, Neural differentiation, Nitrogen, Nonhuman, Organoids, Paraffin, Paraffin embedding, Paraformaldehyde, Patch clamp technique, Penicillin derivative, Phenolsulfonphthalein, Phenotype, Phosphate buffered saline, Phosphoprotein phosphatase inhibitor, Polyacrylamide gel electrophoresis, Potassium chloride, Povidone iodine, Promoter region, Proteinase inhibitor, Real time polymerase chain reaction, Receptor type tyrosine protein phosphatase c, Restriction endonuclease, Retina, Retina dystrophy, Retina regeneration, Retinol, Rhodopsin, Rna extraction, Stem cell, Stem cells, Subcutaneous fat, Tunel assay, Visual impairment, Western blotting


Moreira, VB, Rintjema, J, Bravo, F, Kleij, AW, Franco, L, Puiggalí, J, Alemán, C, Armelin, E, (2022). Novel Biobased Epoxy Thermosets and Coatings from Poly(limonene carbonate) Oxide and Synthetic Hardeners Acs Sustainable Chemistry & Engineering 10, 2708-2719

In the area of coating development, it is extremely difficult to find a substitute for bisphenol A diglycidyl ether (DGEBA), the classical petroleum-based raw material used for the formulation of epoxy thermosets. This epoxy resin offers fast curing reaction with several hardeners and the best thermal and chemical resistance properties for applications in coatings and adhesive technologies. In this work, a new biobased epoxy, derived from poly(limonene carbonate) oxide (PLCO), was combined with polyetheramine and polyamineamide curing agents, offering a spectrum of thermal and mechanical properties, superior to DGEBA-based thermosets. The best formulation was found to be a combination of PLCO and a commercial curing agent (Jeffamine) in a stoichiometric 1:1 ratio. Although PLCO is a solid due to its high molecular weight, it was possible to create a two-component partially biobased epoxy paint without the need of volatile organic compounds (i.e., solvent-free formulation), intended for use in coating technology to partially replace DGEBA-based thermosets.

JTD Keywords: acid, adhesion, epoxy thermoset, mechanical properties, monomer, polycarbonates, polymers, protection, resins, solvent-free paint, thermal properties, Adhesives, Biobased epoxy, Bisphenol-a-diglycidyl ethers, Carbonation, Coating development, Coating technologies, Curing, Curing agents, Epoxy coatings, Epoxy resins, Epoxy thermoset, Epoxy thermosets, Limonene oxide, Mechanical properties, Monoterpenes, Paint, Poly(limonene carbonate) oxide, Solvent free, Solvent-free paint, Thermal properties, Thermosets, Volatile organic compounds


López-Ortiz, M, Zamora, RA, Giannotti, MI, Hu, C, Croce, R, Gorostiza, P, (2022). Distance and Potential Dependence of Charge Transport Through the Reaction Center of Individual Photosynthetic Complexes Small 18, 2104366

Charge separation and transport through the reaction center of photosystem I (PSI) is an essential part of the photosynthetic electron transport chain. A strategy is developed to immobilize and orient PSI complexes on gold electrodes allowing to probe the complex's electron acceptor side, the chlorophyll special pair P700. Electrochemical scanning tunneling microscopy (ECSTM) imaging and current-distance spectroscopy of single protein complex shows lateral size in agreement with its known dimensions, and a PSI apparent height that depends on the probe potential revealing a gating effect in protein conductance. In current-distance spectroscopy, it is observed that the distance-decay constant of the current between PSI and the ECSTM probe depends on the sample and probe electrode potentials. The longest charge exchange distance (lowest distance-decay constant ?) is observed at sample potential 0 mV/SSC (SSC: reference electrode silver/silver chloride) and probe potential 400 mV/SSC. These potentials correspond to hole injection into an electronic state that is available in the absence of illumination. It is proposed that a pair of tryptophan residues located at the interface between P700 and the solution and known to support the hydrophobic recognition of the PSI redox partner plastocyanin, may have an additional role as hole exchange mediator in charge transport through PSI.© 2021 Wiley-VCH GmbH.

JTD Keywords: azurin, current distance decay spectroscopy, cytochrome c(6), electrochemical scanning tunneling microscopy (ecstm), electrochemistry, photosystem i, photosystem-i, plastocyanin, protein electron transfer, recognition, single metalloprotein, single molecules, structural basis, tunneling spectroscopy, 'current, Amino acids, Charge transfer, Chlorine compounds, Chlorophyll, Current distance decay spectroscopy, Decay spectroscopies, Distance decay, Electrochemical scanning tunneling microscopy, Electrochemical scanning tunneling microscopy (ecstm), Electrodes, Electron transfer, Electron transport, Electron transport properties, Gold compounds, Kinetics, Oxidation-reduction, Photosynthesis, Photosystem i, Photosystem i protein complex, Photosystems, Protein electron transfer, Protein electron-transfer, Proteins, Scanning tunneling microscopy, Silver halides, Single molecule, Single molecules


Sans, J, Arnau, M, Sanz, V, Turon, P, Alemán, C, (2022). Polarized Hydroxyapatite: New Insights and Future Perspectives Through Systematic Electrical Characterization at the Interface Advanced Materials Interfaces 9, 2101631

Murar, M, Albertazzi, L, Pujals, S, (2022). Advanced Optical Imaging-Guided Nanotheranostics toward Personalized Cancer Drug Delivery Nanomaterials 12, 399

Nanomedicine involves the use of nanotechnology for clinical applications and holds promise to improve treatments. Recent developments offer new hope for cancer detection, prevention and treatment; however, being a heterogenous disorder, cancer calls for a more targeted treatment approach. Personalized Medicine (PM) aims to revolutionize cancer therapy by matching the most effective treatment to individual patients. Nanotheranostics comprise a combination of therapy and diagnostic imaging incorporated in a nanosystem and are developed to fulfill the promise of PM by helping in the selection of treatments, the objective monitoring of response and the planning of follow-up therapy. Although well-established imaging techniques, such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT), are primarily used in the development of theranostics, Optical Imaging (OI) offers some advantages, such as high sensitivity, spatial and temporal resolution and less invasiveness. Additionally, it allows for multiplexing, using multi-color imaging and DNA barcoding, which further aids in the development of personalized treatments. Recent advances have also given rise to techniques permitting better penetration, opening new doors for OI-guided nanotheranostics. In this review, we describe in detail these recent advances that may be used to design and develop efficient and specific nanotheranostics for personalized cancer drug delivery. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: 5-aminolevulinic acid, cancer, contrast agents, in-vivo, malignant gliomas, multifunctional nanoparticles, nanomedicine, optical imaging, ovarian-cancer, personalized medicine, quantum dots, silica nanoparticles, targeted probes, theranostics, Cancer, Nanomedicine, Optical imaging, Personalized medicine, Superparamagnetic iron-oxide, Theranostics


Boda, SK, Aparicio, C, (2022). Dual keratinocyte-attachment and anti-inflammatory coatings for soft tissue sealing around transmucosal oral implants Biomaterials Science 10, 665-677

Unlike the attachment of soft epithelial skin tissue to penetrating solid natural structures like fingernails and teeth, sealing around percutaneous/permucosal devices such as dental implants is hindered by inflammation and epidermal down growth. Here, we employed a dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium to promote oral epithelial tissue attachment. For minimizing inflammation-triggered epidermal down growth, we coated pristine and oxygen plasma pre-treated polished titanium (pTi) with conjugated linoleic acid (CLA). Further, in order to aid in soft tissue attachment via the formation of hemidesmosomes, adhesive structures by oral keratinocytes, we coated the anionic linoleic acid (LA) adsorbed titanium with cationic cell adhesive peptides (CAP), LamLG3, a peptide derived from Laminin 332, the major extracellular matrix component of the basement membrane in skin tissue and Net1, derived from Netrin-1, a neural chemoattractant capable of epithelial cell attachment via alpha 6 beta 4 integrins. The dual CLA-CAP coatings on pTi were characterized by X-ray photoelectron spectroscopy and dynamic water contact angle measurements. The proliferation of human oral keratinocytes (TERT-2/OKF6) was accelerated on the peptide coated titanium while also promoting the expression of Col XVII and beta-4 integrin, two markers for hemidesmosomes. Simultaneously, CLA coating suppressed the production of inducible nitric oxide synthase (anti-iNOS); a pro-inflammatory M1 marker expressed in lipopolysaccharide (LPS) stimulated murine macrophages (RAW 264.7) and elevated expression of anti-CD206, associated to an anti-inflammatory M2 macrophage phenotype. Taken together, the dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium can help reduce inflammation and promote permucosal/peri-implant soft tissue sealing.

JTD Keywords: Adhesives, Animal, Animals, Anti-inflammatories, Anti-inflammatory agents, Antiinflammatory agent, Biomolecules, Bone, Cell adhesion, Cell-adhesives, Coatings, Conjugated linoleic acid, Conjugated linoleic-acid, Contact angle, Hemidesmosome, Hemidesmosomes, Human, Humans, Hydroxyapatite, Inflammation, Integrins, Keratinocyte, Keratinocytes, Linoleic acid, Macrophages, Mice, Mouse, Nitric oxide, Oral implants, Pathology, Peptides, Skin tissue, Soft tissue, Supplementation, Surface properties, Surface property, Tissue, Titania, Titanium, X ray photoelectron spectroscopy


Guallar-Garrido, S, Almiñana-Rapún, F, Campo-Pérez, V, Torrents, E, Luquin, M, Julián, E, (2022). BCG Substrains Change Their Outermost Surface as a Function of Growth Media Vaccines 10, 40

Mycobacterium bovis bacillus Calmette-Guérin (BCG) efficacy as an immunotherapy tool can be influenced by the genetic background or immune status of the treated population and by the BCG substrain used. BCG comprises several substrains with genetic differences that elicit diverse phenotypic characteristics. Moreover, modifications of phenotypic characteristics can be influenced by culture conditions. However, several culture media formulations are used worldwide to produce BCG. To elucidate the influence of growth conditions on BCG characteristics, five different substrains were grown on two culture media, and the lipidic profile and physico-chemical properties were evaluated. Our results show that each BCG substrain displays a variety of lipidic profiles on the outermost surface depending on the growth conditions. These modifications lead to a breadth of hydrophobicity patterns and a different ability to reduce neutral red dye within the same BCG substrain, suggesting the influence of BCG growth conditions on the interaction between BCG cells and host cells.

JTD Keywords: cell wall, efficacy, glycerol, hydrophobicity, lipid, neutral red, pdim, pgl, protein, strains, viability, virulence, Acylglycerol, Albumin, Article, Asparagine, Bacterial cell wall, Bacterial gene, Bacterium culture, Bcg vaccine, Catalase, Cell wall, Chloroform, Controlled study, Escherichia coli, Gene expression, Genomic dna, Glycerol, Glycerol monomycolate, Hexadecane, Housekeeping gene, Hydrophobicity, Immune response, Immunogenicity, Immunotherapy, Lipid, Lipid fingerprinting, Magnesium sulfate, Mercaptoethanol, Methanol, Methylglyoxal, Molybdatophosphoric acid, Mycobacterium bovis bcg, Neutral red, Nonhuman, Pdim, Petroleum ether, Pgl, Phenotype, Physical chemistry, Real time reverse transcription polymerase chain reaction, Rna 16s, Rna extraction, Rv0577, Staining, Thin layer chromatography, Unclassified drug


Duro-Castano, A, Rodríguez-Arco, L, Ruiz-Pérez, L, De Pace, C, Marchello, G, Noble-Jesus, C, Battaglia, G, (2021). One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles Biomacromolecules 22, 5052-5064

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

JTD Keywords: alpha-amino-acid, hydrogels, leuchs anhydrides, platform, polypeptides, transformation, triggered cargo release, Amino acids, Amphiphilics, Biocompatibility, Biodegradability, Block lengths, Controlled drug delivery, Dimethyl sulfoxide, Ethylene, Gels, Hydrophobicity, Medical nanotechnology, Methionine, Micelles, Morphology, Nanoparticles, One-pot synthesis, Organic solvents, Oxidation, Physiological condition, Polyethylene glycols, Polyethylene oxides, Polymerization, Post-polymerization, Ring-opening polymerization, Scaffolds (biology), Self assembly, Stimuli-responsive properties, Supramolecular chemistry, Supramolecular gels, Supramolecular micelles, Wormlike micelle


Sans, J, Sanz, V, Turon, P, Aleman, C, (2021). Enhanced CO2 Conversion into Ethanol by Permanently Polarized Hydroxyapatite through C-C Coupling Chemcatchem 13, 5025-5033

Vukomanovic, M, Cendra, MD, Baelo, A, Torrents, E, (2021). Nano-engineering stable contact-based antimicrobials: Chemistry at the interface between nano-gold and bacteria Colloids And Surfaces B-Biointerfaces 208, 112083

Contact-based antimicrobials, as antibiotic-free technologies that use non-specific interactions with bacterial cells to exert antimicrobial activity, are a prospective solution in fighting the global issue of bacterial resistance. A very simplified approach to their design considers the direct bonding of cationic guanidine-containing amino acids to the surface of nano-gold carriers. The structure enables antimicrobial activity due to a high density of cationic surface charges. This opens a set of novel questions that are important for their effective engineering, particularly regarding (i) chemistry and events that take place at the interface between NPs and cells, (ii) the direct influence of a charge (and its change) on interactions with bacterial and mammalian cells, and (iii) the stability of structures (and their antimicrobial activity) in the presence of enzymes, which are addressed in this paper. Because of the ability of amino acid-functionalized nano-gold to retain structural and functional activity, even after exposure to a range of physicochemical stimuli, they provide an excellent nanotechnological platform for designing highly effective contact-based antimicrobials and their applications.

JTD Keywords: agents, antibiotic-free technology, arginine, charged amino acids, contact-based antimicrobials, discovery, enzyme-resistant antimicrobials, functionalized gold, peptides, polymers, resistant, Antibiotic-free technology, Charged amino acids, Contact-based antimicrobials, Enzyme-resistant antimicrobials, Functionalized gold, Nanoparticles


Chausse, V, Schieber, R, Raymond, Y, Ségry, B, Sabaté, R, Kolandaivelu, K, Ginebra, MP, Pegueroles, M, (2021). Solvent-cast direct-writing as a fabrication strategy for radiopaque stents Additive Manufacturing 48, 102392

Pérez-Rafael, S, Ivanova, K, Stefanov, I, Puiggalí, J, del Valle, LJ, Todorova, K, Dimitrov, P, Hinojosa-Caballero, D, Tzanov, T, (2021). Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment Acta Biomaterialia 134, 131-143

Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management. Statement of significance: Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.

JTD Keywords: catechol, chronic wounds, dressing materials, inhibition, mechanism, nano-enabled hydrogels, polyphenols, promogran, self-assembling, silver-lignin nanoparticles, systems, tannins, Chronic wounds, Degradation, Dressing materials, Nano-enabled hydrogels, Self-assembling, Silver-lignin nanoparticles, Thiolated hyaluronic acid


Illa, M, Pla, L, Berdún, S, Mir, M, Rivas, L, Dulay, S, Picard-Hagen, N, Samitier, J, Gratacós, E, Eixarch, E, (2021). Miniaturized electrochemical sensors to monitor fetal hypoxia and acidosis in a pregnant sheep model Biomedicines 9, 1344

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model.

JTD Keywords: continuous monitoring of acid-base status, diagnosis, doppler, electrochemical sensors, growth restriction, high-risk pregnancies, human-fetus, management, responses, tissue ph, Continuous monitoring of acid-base status, Electrochemical sensors, High-risk pregnancies, Umbilical cord occlusion, Umbilical-cord occlusion


Rial-Hermida, MI, Rey-Rico, A, Blanco-Fernandez, B, Carballo-Pedrares, N, Byrne, EM, Mano, JF, (2021). Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules Acs Biomaterials Science & Engineering 7, 4102-4127

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields. © 2021 American Chemical Society.

JTD Keywords: biodegradable dextran hydrogels, biotherapeutics, bone morphogenetic protein-2, carrageenan-based hydrogels, chitosan-based hydrogels, controlled delivery, controlled-release, cross-linked hydrogels, growth-factor delivery, hydrogels, in-vitro characterization, polysaccharides, self-healing hydrogel, stimuli-responsiveness, tissue engineering, Antibodies, Bioactivity, Biodegradability, Biomedical fields, Biomolecules, Biotherapeutics, Chemical modification, Circular economy, Controlled delivery, Controlled drug delivery, Delivery systems, Drug delivery system, Functional polymers, Hyaluronic-acid hydrogels, Hydrogels, Industrial processs, Polysaccharides, Recent progress, Renewable sources, Stimuli-responsiveness, Targeted drug delivery, Tissue engineering, Waste management


Villasante, A, Robinson, STT, Cohen, ARR, Lock, R, Guo, XE, Vunjak-Novakovic, G, (2021). Human Serum Enhances Biomimicry of Engineered Tissue Models of Bone and Cancer Frontiers In Bioengineering And Biotechnology 9, 658472

For decades, fetal bovine serum (FBS) has been used routinely for culturing many cell types, based on its empirically demonstrated effects on cell growth, and the lack of suitable non-xenogeneic alternatives. The FBS-based culture media do not represent the human physiological conditions, and can compromise biomimicry of preclinical models. To recapitulate in vitro the features of human bone and bone cancer, we investigated the effects of human serum and human platelet lysate on modeling osteogenesis, osteoclastogenesis, and bone cancer in two-dimensional (2D) and three-dimensional (3D) settings. For monitoring tumor growth within tissue-engineered bone in a non-destructive fashion, we generated cancer cell lines expressing and secreting luciferase. Culture media containing human serum enhanced osteogenesis and osteoclasts differentiation, and provided a more realistic in vitro mimic of human cancer cell proliferation. When human serum was used for building 3D engineered bone, the tissue recapitulated bone homeostasis and response to bisphosphonates observed in native bone. We found disparities in cell behavior and drug responses between the metastatic and primary cancer cells cultured in the bone niche, with the effectiveness of bisphosphonates observed only in metastatic models. Overall, these data support the utility of human serum for bioengineering of bone and bone cancers.

JTD Keywords: 3d cancer models, 3rs, alpha tnf-alpha, culture, cypridina luciferase, ewings-sarcoma, ewing’s sarcoma, human platelet lysate, human serum, human tumor, in-vitro, osteogenic differentiation, stem-cells, zoledronic acid, 3d cancer models, 3rs, Cypridina luciferase, Ewing's sarcoma, Ewing’s sarcoma, Fetal bovine serum, Human serum


Roki, N, Solomon, M, Casta, L, Bowers, J, Getts, RC, Muro, S, (2021). A method to improve quantitative radiotracing-based analysis of the in vivo biodistribution of drug carriers Bioeng Transl Med 6, e210208

© 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers. Biodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free-label signal may arise prior to or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle. First, we verified free signal generation in animal samples and then, mimicking it in a controllable setting, we injected mice intravenously with a radiolabeled drug carrier formulation (125I-antibody/3DNA) containing a known amount of free radiolabel (125I), or free 125I alone as a control. Corrected biodistribution data were obtained by separating the free radiolabel from blood and organs postmortem, using trichloroacetic acid precipitation, and subtracting the confounding signal from each tissue measurement. Control free 125I-radiolabel was detected at ≥85% accuracy in blood and tissues, validating the method. It biodistributed very heterogeneously among organs (0.6–39 %ID/g), indicating that any free 125I generated in the body or present in an injected formulation cannot be simply corrected to the free-label fraction in the original preparation, but the free label must be empirically measured in each organ. Application of this method to the biodistribution of 125I-antibody/3DNA, including formulations directed to endothelial target ICAM-1, showed accurate classification of free 125I species in blood and tissues. In addition, this technique rendered data on the in vivo degradation of the traced agents over time. Thus, this is a valuable technique to obtain accurate measurements of biodistribution using 125I and possibly other radiotracers.

JTD Keywords: biodistribution data correction, degradation, drug delivery carriers, free label, in vivo biodistribution, radiotracing, trichloroacetic acid precipitation, Biodistribution data correction, Degradation, Drug delivery carriers, Free label, In vivo biodistribution, Radiotracing, Trichloroacetic acid precipitation


Sans, J, Sanz, V, del Valle, LJ, Puiggali, J, Turon, P, Aleman, C, (2021). Optimization of permanently polarized hydroxyapatite catalyst. Implications for the electrophotosynthesis of amino acids by nitrogen and carbon fixation Journal Of Catalysis 397, 98-107

The enhanced catalytic activity of permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, largely depends on both the experimental conditions used to prepare crystalline hydroxyapatite from its calcium and phosphate precursors and the polarization process parameters. A mineral similar to brushite, which is an apatitic phase that can evolve to hydroxyapatite, is found at the surface of highly crystalline hydroxyapatite. It appears after chemical precipitation and hydrothermal treatment performed at 150 degrees C for 24 h followed by a sinterization at 1000 degrees C and a polarization treatment by applying a voltage of 500 Vat high temperature. Both the high crystallinity and the presence of brushite-like phase on the electrophotocatalyst affect the nitrogen and carbon fixation under mild reaction conditions (95 degrees C and 6 bar) and the synthesis of glycine and alanine from a simple gas mixture containing N-2, CO2, CH4 and H2O. Thus, the Gly/Ala ratio can be customized by controlling the presence of brushite on the surface of the catalyst, enabling to develop new strategies to regulate the production of amino acids by nitrogen and carbon fixation. (C) 2021 Elsevier Inc. All rights reserved.

JTD Keywords: Amino acids, Brushite, Carbon, Carbon dioxide fixation, Catalyst activity, Catalytic apatites, Chemical precipitation, Crystalline hydroxyapatite, Crystallinity, Decomposition, Enhanced catalytic activity, Experimental conditions, Heterogeneous catalysis, High crystallinity, Hydrothermal synthesis, Hydrothermal treatments, Hydroxyapatite, Lactic-acid, Mild reaction conditions, Molecular nitrogen fixation, Nitrogen, Nitrogen fixation, Phosphate, Polarization, Precipitation (chemical), Process parameters, Thermally stimulated polarization


Trebicka, J, Bork, P, Krag, A, Arumugam, M, (2021). Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure Nature Reviews Gastroenterology & Hepatology 18, 167-180

© 2020, Springer Nature Limited. The human gut microbiome has emerged as a major player in human health and disease. The liver, as the first organ to encounter microbial products that cross the gut epithelial barrier, is affected by the gut microbiome in many ways. Thus, the gut microbiome might play a major part in the development of liver diseases. The common end stage of liver disease is decompensated cirrhosis and the further development towards acute-on-chronic liver failure (ACLF). These conditions have high short-term mortality. There is evidence that translocation of components of the gut microbiota, facilitated by different pathogenic mechanisms such as increased gut epithelial permeability and portal hypertension, is an important driver of decompensation by induction of systemic inflammation, and thereby also ACLF. Elucidating the role of the gut microbiome in the aetiology of decompensated cirrhosis and ACLF deserves further investigation and improvement; and might be the basis for development of diagnostic and therapeutic strategies. In this Review, we focus on the possible pathogenic, diagnostic and therapeutic role of the gut microbiome in decompensation of cirrhosis and progression to ACLF.

JTD Keywords: albumin, decreases intestinal permeability, hepatic-encephalopathy, portal-vein thrombosis, rifaximin improves, secondary bile-acids, systemic inflammation, translocation, venous-pressure gradient, Spontaneous bacterial peritonitis


Rubi-Sans, G, Cano-Torres, I, Perez-Amodio, S, Blanco-Fernandez, B, Mateos-Timoneda, MA, Engel, E, (2021). Development and Angiogenic Potential of Cell-Derived Microtissues Using Microcarrier-Template Biomedicines 9, 232

Tissue engineering and regenerative medicine approaches use biomaterials in combination with cells to regenerate lost functions of tissues and organs to prevent organ transplantation. However, most of the current strategies fail in mimicking the tissue's extracellular matrix properties. In order to mimic native tissue conditions, we developed cell-derived matrix (CDM) microtissues (MT). Our methodology uses poly-lactic acid (PLA) and Cultispher(R) S microcarriers' (MCs') as scaffold templates, which are seeded with rat bone marrow mesenchymal stem cells (rBM-MSCs). The scaffold template allows cells to generate an extracellular matrix, which is then extracted for downstream use. The newly formed CDM provides cells with a complex physical (MT architecture) and biochemical (deposited ECM proteins) environment, also showing spontaneous angiogenic potential. Our results suggest that MTs generated from the combination of these two MCs (mixed MTs) are excellent candidates for tissue vascularization. Overall, this study provides a methodology for in-house fabrication of microtissues with angiogenic potential for downstream use in various tissue regenerative strategies.

JTD Keywords: angiogenesis, cell-derived matrix, cultispher® s, microtissue, poly-lactic acid microcarriers, Angiogenesis, Cell-derived matrix, Cultispher (r) s, Cultispher® s, Microtissue, Poly-lactic acid microcarriers, Rat bone marrow mesenchymal stem cells


Pla, L, Berdún, S, Mir, M, Rivas, L, Miserere, S, Dulay, S, Samitier, J, Eixarch, E, Illa, M, Gratacós, E, (2021). Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia Journal Of Translational Medicine 19, 53

© 2021, The Author(s). Background: One of the most prevalent causes of fetal hypoxia leading to stillbirth is placental insufficiency. Hemodynamic changes evaluated with Doppler ultrasound have been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. As a first step, the present work aimed to evaluate the performance of miniaturized electrochemical sensors in the continuous monitoring of oxygen and pH changes in a model of acute hypoxia-acidosis. Methods: pH and oxygen electrochemical sensors were evaluated in a ventilatory hypoxia rabbit model. The ventilator hypoxia protocol included 3 differential phases: basal (100% FiO2), the hypoxia-acidosis period (10% FiO2) and recovery (100% FiO2). Sensors were tested in blood tissue (ex vivo sensing) and in muscular tissue (in vivo sensing). pH electrochemical and oxygen sensors were evaluated on the day of insertion (short-term evaluation) and pH electrochemical sensors were also tested after 5 days of insertion (long-term evaluation). pH and oxygen sensing were registered throughout the ventilatory hypoxia protocol (basal, hypoxia-acidosis, and recovery) and were compared with blood gas metabolites results from carotid artery catheterization (obtained with the EPOC blood analyzer). Finally, histological assessment was performed on the sensor insertion site. One-way ANOVA was used for the analysis of the evolution of acid-based metabolites and electrochemical sensor signaling results; a t-test was used for pre- and post-calibration analyses; and chi-square analyses for categorical variables. Results: At the short-term evaluation, both the pH and oxygen electrochemical sensors distinguished the basal and hypoxia-acidosis periods in both the in vivo and ex vivo sensing. However, only the ex vivo sensing detected the recovery period. In the long-term evaluation, the pH electrochemical sensor signal seemed to lose sensibility. Finally, histological assessment revealed no signs of alteration on the day of evaluation (short-term), whereas in the long-term evaluation a sub-acute inflammatory reaction adjacent to the implantation site was detected. Conclusions: Miniaturized electrochemical sensors represent a new generation of tools for the continuous monitoring of hypoxia-acidosis, which is especially indicated in high-risk pregnancies. Further studies including more tissue-compatible material would be required in order to improve long-term electrochemical sensing.

JTD Keywords: acute hypoxia-acidosis, continuous monitoring of acid-base status, continuous monitoring of acid–base status, electrochemical sensors, high-risk pregnancies, Acute hypoxia-acidosis, Continuous monitoring of acid–base status, Electrochemical sensors, High-risk pregnancies


Dhillon, P, Park, J, del Pozo, CH, Li, LZ, Doke, T, Huang, SZ, Zhao, JJ, Kang, HM, Shrestra, R, Balzer, MS, Chatterjee, S, Prado, P, Han, SY, Liu, HB, Sheng, X, Dierickx, P, Batmanov, K, Romero, JP, Prósper, F, Li, MY, Pei, LM, Kim, J, Montserrat, N, Susztak, K, (2021). The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation Cell Metabolism 33, 379-394.e8

© 2020 Elsevier Inc. Using single-cell RNA sequencing, Susztak and colleagues, show major changes in cell diversity in mouse models of kidney fibrosis. Proximal tubule (PT) cells are highly vulnerable to dysfunction in fibrosis and show altered differentiation. Nuclear receptors such as ESRRA maintain both PT cell metabolism and differentiation by directly regulating PT-cell-specific genes.

JTD Keywords: chronic kidney disease, esrra, fatty-acid oxidation, fibrosis, kidney, organoids, ppara, proximal tubule cells, single-cell atac sequencing, Chronic kidney disease, Esrra, Fatty-acid oxidation, Fibrosis, Kidney, Organoids, Ppara, Proximal tubule cells, Single-cell atac sequencing, Single-cell rna sequencing


Marrugo-Ramírez, J, Rodríguez-Núñez, M, Marco, MP, Mir, M, Samitier, J, (2021). Kynurenic Acid Electrochemical Immunosensor: Blood-Based Diagnosis of Alzheimer's Disease Biosensors 11, 20

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by a functional deterioration of the brain. Currently, there are selected biomarkers for its diagnosis in cerebrospinal fluid. However, its extraction has several disadvantages for the patient. Therefore, there is an urgent need for a detection method using sensitive and selective blood-based biomarkers. Kynurenic acid (KYNA) is a potential biomarker candidate for this purpose. The alteration of the KYNA levels in blood has been related with inflammatory processes in the brain, produced as a protective function when neurons are damaged. This paper describes a novel electrochemical immunosensor for KYNA detection, based on successive functionalization multi-electrode array. The resultant sensor was characterized by cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). The proposed biosensor detects KYNA within a linear calibration range from 10 pM to 100 nM using CA and EIS, obtaining a limit of detection (LOD) of 16.9 pM and 37.6 pM in buffer, respectively, being the lowest reported LOD for this biomarker. Moreover, to assess our device closer to the real application, the developed immunosensor was also tested under human serum matrix, obtaining an LOD of 391.71 pM for CA and 278.8 pM for EIS with diluted serum.

JTD Keywords: alzheimer’s disease (ad), blood analysis, chronoamperometry (ca), electrochemical biosensor, electrochemical impedance spectroscopy (eis), immunosensor, in vitro diagnosis (ivd), kynurenic acid (kyna), Alzheimer’s disease (ad), Blood analysis, Chronoamperometry (ca), Electrochemical biosensor, Electrochemical impedance spectroscopy (eis), Immunosensor, In vitro diagnosis (ivd), Kynurenic acid (kyna), Point of care diagnosis (poc)


Morgese, G., de Waal, B. F. M., Varela-Aramburu, S., Palmans, A. R. A., Albertazzi, L., Meijer, E. W., (2020). Anchoring supramolecular polymers to human red blood cells by combining dynamic covalent and non-covalent chemistries Angewandte Chemie - International Edition 59, (39), 17229-17233

Understanding cell/material interactions is essential to design functional cell-responsive materials. While the scientific literature abounds with formulations of biomimetic materials, only a fraction of them focused on mechanisms of the molecular interactions between cells and material. To provide new knowledge on the strategies for materials/cell recognition and binding, supramolecular benzene-1,3,5-tricarboxamide copolymers bearing benzoxaborole moieties are anchored on the surface of human erythrocytes via benzoxaborole/sialic-acid binding. This interaction based on both dynamic covalent and non-covalent chemistries is visualized in real time by means of total internal reflection fluorescence microscopy. Exploiting this imaging method, we observe that the functional copolymers specifically interact with the cell surface. An optimal fiber affinity towards the cells as a function of benzoxaborole concentration demonstrates the crucial role of multivalency in these cell/material interactions.

JTD Keywords: Boronic acid, Cell/material interactions, Multivalency, Red blood cells, Supramolecular polymers


Sans, J., Armelin, E., Sanz, V., Puiggalí, J., Turon, P., Alemán, C., (2020). Breaking-down the catalyst used for the electrophotosynthesis of amino acids by nitrogen and carbon fixation Journal of Catalysis 389, 646-656

The electrophotocatalytic synthesis of Glycine and Alanine from a simple gas mixture containing N2, CO2, CH4 and H2O under mild reaction conditions (95 °C and 6 bar) was recently developed using a catalyst formed by permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, coated with two layers of aminotris(methylenephosphonic acid) (ATMP) separated by an intermediate layer of zirconyl chloride (ZC). This work reports the optimization of the ATMP- and ZC-coating content by examining the influence of their concentration of each component in each layer on the structural and electrochemical properties of the catalyst. After exhaustive analyses, such properties have been related with the efficiency of the catalysts prepared using different ATMP- and ZC-concentrations to yield Gly and Ala amino acids by fixing nitrogen from N2 and carbon from CO2 and CH4. Results show that, although the concentrations of ATMP and ZC in the first and the intermediate layers are important, the third layer plays a predominant role as is responsible of the apparition of supramolecular structures on the surface and the capacitive behavior of the coating

JTD Keywords: Carbon dioxide fixation, Electrocatalyst, Heterogeneous catalysis, Phosphonic acid, Photocatalyst, Polarized hydroxyapatite, Surface chemistry, Zirconyl chloride


Molina, B. G., Lopes-Rodrigues, M., Estrany, F., Michaux, C., Perpète, E. A., Armelin, E., Alemán, C., (2020). Free-standing flexible and biomimetic hybrid membranes for ions and ATP transport Journal of Membrane Science 601, 117931

The transport of metabolites across robust, flexible and free-standing biomimetic membranes made of three perforated poly (lactic acid) (pPLA) layers, separated by two anodically polymerized conducting layers of poly (3,4-ethylenedioxythiophene-co-3-dodecylthiophene), and functionalized on the external pPLA layers with a voltage dependent anion channel (VDAC) protein, has been demonstrated. The three pPLA layers offer robustness and flexibility to the bioactive platform and the possibility of obtaining conducing polymer layers by in situ anodic polymerization. The incorporation of dodecylthiophene units, which bear a 12 carbon atoms long linear alkyl chain, to the conducting layers allows mimicking the amphiphilic environment offered by lipids in cells, increasing 32% the efficiency of the functionalization. Electrochemical impedance measurements in NaCl and adenosine triphosphate (ATP) solutions prove that the integration of the VDAC porin inside the PLA perforations considerably increases the membrane conductivity and is crucial for the electrolyte diffusion. Such results open the door for the development of advanced sensing devices for a broad panel of biomedical applications.

JTD Keywords: Conducting polymers, Membrane proteins, Membranes, Polylactic acid, Self-supported films


Romero-Montero, A., del Valle, L. J., Puiggalí, J., Montiel, C., García-Arrazola, R., Gimeno, M., (2020). Poly(gallic acid)-coated polycaprolactone inhibits oxidative stress in epithelial cells Materials Science and Engineering C 115, 111154

Enzymatic mediated poly (gallic acid) (PGAL), a stable multiradical polyanion with helicoidal secondary structure and high antioxidant capacity, was successfully grafted to poly(ε-caprolactone) (PCL) using UV-photo induction. PCL films were prepared with several levels of roughness and subsequently grafted with PGAL (PCL-g-PGAL). The results on the full characterization of the produced materials by mechanical tests, surface morphology, and topography, thermal and crystallographic analyses, as well as wettability and cell protection activity against oxidative stress, were adequate for tissue regeneration. The in vitro biocompatibility was then assessed with epithelial-like cells showing excellent adhesion and proliferation onto the PCL-g-PGAL films, most importantly, PCL-g-PGAL displayed a good ability to protect cell cultures on their surface against reactive oxygen species. These biomaterials can consequently be considered as novel biocompatible and antioxidant films with high-responsiveness for biomedical or tissue engineering applications.

JTD Keywords: Antioxidant, Poly(gallic acid), Polyphenol, Radical oxygen species


Moghimiardekani, A., Molina, B. G., Enshaei, H., del Valle, L. J., Pérez-Madrigal, M. M., Estrany, F., Alemán, C., (2020). Semi-interpenetrated hydrogels-microfibers electroactive assemblies for release and real-time monitoring of drugs Macromolecular Bioscience 20, (7), 2000074

Simultaneous drug release and monitoring using a single polymeric platform represents a significant advance in the utilization of biomaterials for therapeutic use. Tracking drug release by real-time electrochemical detection using the same platform is a simple way to guide the dosage of the drug, improve the desired therapeutic effect, and reduce the adverse side effects. The platform developed in this work takes advantage of the flexibility and loading capacity of hydrogels, the mechanical strength of microfibers, and the capacity of conducting polymers to detect the redox properties of drugs. The engineered platform is prepared by assembling two spin-coated layers of poly-γ-glutamic acid hydrogel, loaded with poly(3,4-ethylenedioxythiophene) (PEDOT) microparticles, and separated by a electrospun layer of poly-ε-caprolactone microfibers. Loaded PEDOT microparticles are used as reaction nuclei for the polymerization of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT), that semi-interpenetrate the whole three layered system while forming a dense network of electrical conduction paths. After demonstrating its properties, the platform is loaded with levofloxacin and its release monitored externally by UV–vis spectroscopy and in situ by using the PHMeDOT network. In situ real-time electrochemical monitoring of the drug release from the engineered platform holds great promise for the development of multi-functional devices for advanced biomedical applications.

JTD Keywords: Biosensors, Conducting polymers, Drug delivery, Poly-γ-glutamic acid, Poly-ε-caprolactone


Blanco-Cabra, N., Vega-Granados, K., Moya-Andérico, L., Vukomanovic, M., Parra, A., Álvarez De Cienfuegos, L., Torrents, E., (2019). Novel oleanolic and maslinic acid derivatives as a promising treatment against Bacterial biofilm in nosocomial infections: An in vitro and in vivo study ACS Infectious Diseases 5, (9), 1581-1589

Oleanolic acid (OA) and maslinic acid (MA) are pentacyclic triterpenic compounds that abound in industrial olive oil waste. These compounds have renowned antimicrobial properties and lack cytotoxicity in eukaryotic cells as well as resistance mechanisms in bacteria. Despite these advantages, their antimicrobial activity has only been tested in vitro, and derivatives improving this activity have not been reported. In this work, a set of 14 OA and MA C-28 amide derivatives have been synthesized. Two of these derivatives, MA-HDA and OA-HDA, increase the in vitro antimicrobial activity of the parent compounds while reducing their toxicity in most of the Gram-positive bacteria tested, including a methicillin-resistant Staphylococcus aureus-MRSA. MA-HDA also shows an enhanced in vivo efficacy in a Galleria mellonella invertebrate animal model of infection. A preliminary attempt to elucidate their mechanism of action revealed that these compounds are able to penetrate and damage the bacterial cell membrane. More significantly, their capacity to reduce antibiofilm formation in catheters has also been demonstrated in two sets of conditions: a static and a more challenged continuous-flow S. aureus biofilm.

JTD Keywords: Antibiofilm, Galleria mellonella, In vitro and in vivo antimicrobials, Maslinic and oleanolic acids, Natural products, Staphylococcus aureus


de la Mata, Ana, Mateos-Timoneda, Miguel A., Nieto-Miguel, Teresa, Galindo, Sara, López-Paniagua, Marina, Planell, Josep A., Engel, Elisabeth, Calonge, Margarita, (2019). Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells Colloids and Surfaces B: Biointerfaces 177, 121-129

Limbal epithelial stem cells (LESCs) are responsible for the renewal of corneal epithelium. Cultivated limbal epithelial transplantation is the current treatment of choice for restoring the loss or dysfunction of LESCs. To perform this procedure, a substratum is necessary for in vitro culturing of limbal epithelial cells and their subsequent transplantation onto the ocular surface. In this work, we evaluated poly-L/DL-lactic acid 70:30 (PLA) films functionalized with type IV collagen (col IV) as potential in vitro carrier substrata for LESCs. We first demonstrated that PLA-col IV films were biocompatible and suitable for the proliferation of human corneal epithelial cells. Subsequently, limbal epithelial cell suspensions, isolated from human limbal rings, were cultivated using culture medium that did not contain animal components. The cells adhered significantly faster to PLA-col IV films than to tissue culture plastic (TCP). The mRNA expression levels for the LESC specific markers, K15, P63α and ABCG2 were similar or greater (significantly in the case of K15) in limbal epithelial cells cultured on PLA-col IV films than limbal epithelial cells cultured on TCP. The percentage of cells expressing the corneal (K3, K12) and the LESC (P63α, ABCG2) specific markers was similar for both substrata. These results suggest that the PLA-col IV films promoted LESC attachment and helped to maintain their undifferentiated stem cell phenotype. Consequently, these substrata offer an alternative for the transplantation of limbal cells onto the ocular surface.

JTD Keywords: Corneal epithelium, Collagen IV, Limbal stem cells, Polylactic acid, Tissue engineering


Casanellas, Ignasi, Lagunas, Anna, Vida, Yolanda, Pérez-Inestrosa, Ezequiel, Andrades, José A., Becerra, José, Samitier, Josep, (2019). Matrix nanopatterning regulates mesenchymal differentiation through focal adhesion size and distribution according to cell fate Biomimetics Biomimetic Nanotechnology for Biomedical Applications (NanoBio&Med 2018) , MDPI (Barcelona, Spain) 4, (2), 43

Extracellular matrix remodeling plays a pivotal role during mesenchyme patterning into different lineages. Tension exerted from cell membrane receptors bound to extracellular matrix ligands is transmitted by the cytoskeleton to the cell nucleus inducing gene expression. Here, we used dendrimer-based arginine–glycine–aspartic acid (RGD) uneven nanopatterns, which allow the control of local surface adhesiveness at the nanoscale, to unveil the adhesive requirements of mesenchymal tenogenic and osteogenic commitments. Cell response was found to depend on the tension resulting from cell–substrate interactions, which affects nuclear morphology and is regulated by focal adhesion size and distribution.

JTD Keywords: Arginine–glycine–aspartic acid (RGD), Nanopattern, Mesenchymal stem cells, Tenogenesis, Osteogenesis, Cell nuclei, Focal adhesions


Casanellas, Ignasi, Lagunas, Anna, Tsintzou, Iro, Vida, Yolanda, Collado, Daniel, Pérez-Inestrosa, Ezequiel, Rodríguez-Pereira, Cristina, Magalhaes, Joana, Gorostiza, Pau, Andrades, José A., Becerra, José, Samitier, Josep, (2018). Dendrimer-based uneven nanopatterns to locally control surface adhesiveness: A method to direct chondrogenic differentiation Journal of Visualized Experiments Bioengineering, (131), e56347

Cellular adhesion and differentiation is conditioned by the nanoscale disposition of the extracellular matrix (ECM) components, with local concentrations having a major effect. Here we present a method to obtain large-scale uneven nanopatterns of arginine-glycine-aspartic acid (RGD)-functionalized dendrimers that permit the nanoscale control of local RGD surface density. Nanopatterns are formed by surface adsorption of dendrimers from solutions at different initial concentrations and are characterized by water contact angle (CA), X-ray photoelectron spectroscopy (XPS), and scanning probe microscopy techniques such as scanning tunneling microscopy (STM) and atomic force microscopy (AFM). The local surface density of RGD is measured using AFM images by means of probability contour maps of minimum interparticle distances and then correlated with cell adhesion response and differentiation. The nanopatterning method presented here is a simple procedure that can be scaled up in a straightforward manner to large surface areas. It is thus fully compatible with cell culture protocols and can be applied to other ligands that exert concentration-dependent effects on cells.

JTD Keywords: Bioengineering, Dendrimer, Nanopattern, Arginine-Glycine-Aspartic Acid (RGD), Atomic Force Microscopy (AFM), Cell Adhesion, Mesenchymal Stem Cells (Mscs), Chondrogenesis


Barbeck, Mike, Serra, Tiziano, Booms, Patrick, Stojanovic, Sanja, Najman, Stevo, Engel, Elisabeth, Sader, Robert, Kirkpatrick, Charles James, Navarro, Melba, Ghanaati, Shahram, (2017). Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components – Guidance of the inflammatory response as basis for osteochondral regeneration Bioactive Materials , 2, (4), 208-223

Abstract The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the (molecular) weight loss and the morphological and mechanical variations after immersion in SBF. The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods. Both scaffold parts kept their structural integrity, while changes in morphology were observed, especially for the PLA/G5 scaffold. Mechanical properties decreased with progressive degradation, while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds. The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds, while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization. Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers. Altogether, the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength. Furthermore, the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs, while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration. Thus, this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects. Additionally, the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.

JTD Keywords: Bioactive glass, Polylactic acid (PLA), Bi-layer scaffold, Multinucleated giant cells, Bone substitute, Vascularization, Calcium phosphate glass


Moles, E., Marcos, J., Imperial, S., Pozo, O. J., Fernàndez-Busquets, X., (2017). 2-picolylamine derivatization for high sensitivity detection of abscisic acid in apicomplexan blood-infecting parasites Talanta 168, 130-135

We have developed a new liquid chromatography-electrospray ionization tandem mass spectrometry methodology based on 2-picolylamine derivatization and positive ion mode detection for abscisic acid (ABA) identification. The selected reaction leads to the formation of an amide derivative which contains a highly active pyridyl group. The enhanced ionization allows for a 700-fold increase over commonly monitored unmodified ABA, which in turn leads to excellent limits of detection and quantification values of 0.03 and 0.15 ng mL-1, respectively. This method has been validated in the highly complex matrix of a red blood cell extract. In spite of the high sensitivity achieved, ABA could not be detected in Plasmodium falciparum-infected red blood cells, suggesting that, if present, it will be found either in ultratrace amounts or as brief bursts at defined time points within the intraerythrocytic cycle and/or in the form of a biosynthetic analogue.

JTD Keywords: Abscisic acid, Apicomplexa, Liquid chromatography-electrospray ionization tandem mass spectrometry, Malaria, Picolylamine, Plasmodium falciparum


Gugutkov, D., Gustavsson, J., Cantini, M., Salmeron-Sánchez, M., Altankov, G., (2017). Electrospun fibrinogen-PLA nanofibres for vascular tissue engineering Journal of Tissue Engineering and Regenerative Medicine 11, (10), 2774-2784

Here we report on the development of a new type of hybrid fibrinogen-polylactic acid (FBG-PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate-like morphology with multiple projections. The well-developed focal adhesion complexes suggested a successful cellular interaction. However, time-lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time-lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization.

JTD Keywords: Electrospun nanofibers, Endothelial cells, Fibrinogen, Guided cellular behavior, Polylactic acid, Vascular tissue engineering


Punet, X., Levato, R., Bataille, I., Letourneur, D., Engel, E., Mateos-Timoneda, M. A., (2017). Polylactic acid organogel as versatile scaffolding technique Polymer 113, 81-91

Tissue engineering requires scaffolding techniques based on non-toxic processes that permits the fabrication of constructs with tailored properties. Here, a two-step methodology based on the gelation and precipitation of the poly(lactic) acid/ethyl lactate organogel system is presented. With this technique nanofibrous matrices that resemble natural extracellular matrix can be easily obtained, while allowing control over the mechanical properties of the device. Gelation temperature and the dynamics of the gelation of the organogel system are characterized, and the final mechanical and viscoelastic properties, as well as porosity, as function of the initial polymer concentration are described. We show that gelation temperature of the system is concentration independent and below 44.5 °C, which permits gelation at room temperature. Furthermore, mechanical properties are found in the range of the soft organic tissues, and the obtained micro-network architecture gives place to a flexible structure. Such structure presents tuneable elastic modulus and viscoelastic properties as function of nanofibers density. Moreover, centimetre-long tubular scaffolds with the diameter of medium-caliber blood vessels were produced. The fibrous nano-architecture mimics the native extracellular matrix fibres diameter and morphology was proven to be suitable to support endothelialization of the lumen of the tube. Thus, this strategy, based on biocompatible green compound might be promising for the fabrication of large 3D scaffolds for tissue engineering applications.

JTD Keywords: Gel, Gelation, Nanofibrous, Organogel, PLA, Poly(lactic) acid, Scaffold


Manca, M. L., Castangia, I., Zaru, M., Nácher, A., Valenti, D., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2015). Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring Biomaterials 71, 100-109

In the present work new highly biocompatible nanovesicles were developed using polyanion sodium hyaluronate to form polymer immobilized vesicles, so called hyalurosomes. Curcumin, at high concentration was loaded into hyalurosomes and physico-chemical properties and in vitro/in vivo performances of the formulations were compared to those of liposomes having the same lipid and drug content. Vesicles were prepared by direct addition of dispersion containing the polysaccharide sodium hyaluronate and the polyphenol curcumin to a commercial mixture of soy phospholipids, thus avoiding the use of organic solvents. An extensive study was carried out on the physico-chemical features and properties of curcumin-loaded hyalurosomes and liposomes. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that vesicles were spherical, uni- or oligolamellar and small in size (112-220 nm). The in vitro percutaneous curcumin delivery studies on intact skin showed an improved ability of hyalurosomes to favour a fast drug deposition in the whole skin. Hyalurosomes as well as liposomes were biocompatible, protected in vitro human keratinocytes from oxidative stress damages and promoted tissue remodelling through cellular proliferation and migration. Moreover, in vivo tests underlined a good effectiveness of curcumin-loaded hyalurosomes to counteract 12-O-tetradecanoilphorbol (TPA)-produced inflammation and injuries, diminishing oedema formation, myeloperoxydase activity and providing an extensive skin reepithelization. Thanks to the one-step and environmentally-friendly preparation method, component biocompatibility and safety, good in vitro and in vivo performances, the hyalurosomes appear as promising nanocarriers for cosmetic and pharmaceutical applications.

JTD Keywords: Cell oxidative stress, Hyaluronic acid/Hyaluronan, Phospholipid vesicles, Polyphenols, Skin inflammation, Wound healing


Keremidarska, M., Gugutkov, D., Altankov, G., Krasteva, N., (2015). Impact of electrospun nanofibres orientation on mesenchymal stem cell adhesion and morphology Comptes Rendus de L'Academie Bulgare des Sciences , 68, (10), 1271-1276

Electrospun nanofibrous materials mimicking the architecture of native extracellular matrix (ECM) hold great promise as scaffolds in tissue engineering. In order to optimize the properties of nanofibrous scaffolds it is important to understand the impact of fibres’ organization on cell behaviour. Herein, we investigated the effect of nanofibres (NFs) alignment on human adipose-derived mesenchymal stem cells (hAD-MSCs) adhesion and morphology. Electrospun composite fibrinogen/poly-lactic acid (FNG/PLA) NF scaffolds with same composition and comparable fibre size were fabricated into randomly oriented and aligned configuration and stem cells adhesion was characterized by the meaning of overall cell morphology, actin cytoskeleton organization and expression of molecules, involved in the development of focal adhesion complexes. We found that hAD-MSCs altered their morphology, actin cytoskeleton and cell attachment in accordance with nanofibre orientation while cell spreading, focal adhesions and expression of β1 and αNintegrin receptors were not influenced significantly by fibre orientation. These results confirmed that fibre alignment of scaffold guide cellular arrangement and could be beneficial for stem differentiation and therefore for the successful scaffolds development if its contact guidance coincided with the cell shape and cytoskeletal tension.

JTD Keywords: Electrospinning, Fibrinogen/polylactic acid hybrid nanofibres, Human adipose-derived stem cells


Cuervo, A., Dans, P. D., Carrascosa, J. L., Orozco, M., Gomila, G., Fumagalli, L., (2014). Direct measurement of the dielectric polarization properties of DNA Proceedings of the National Academy of Sciences of the United States of America 111, (35), E3624-E3630

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ~ 2–4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.

JTD Keywords: Atomic force microscopy, Atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, capsid protein, DNA, double stranded DNA, amino acid composition, article, atomic force microscopy, bacteriophage, bacteriophage T7, dielectric constant, dipole, DNA binding, DNA packaging, DNA structure, electron microscopy, ligand binding, nonhuman, polarization, priority journal, protein analysis, protein DNA interaction, scanning probe microscopy, static electricity, virion, virus capsid, virus particle, atomic force microscopy, atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, Bacteriophage T7, Capsid, Cations, Dielectric Spectroscopy, DNA, DNA, Viral, DNA-Binding Proteins, Electrochemical Techniques, Ligands, Microscopy, Atomic Force, Models, Chemical, Nuclear Proteins


Lagunas, A., Garcia, A., Artés, J. M., Vida, Y., Collado, D., Pérez-Inestrosa, E., Gorostiza, P., Claros, S., Andrades, J. A., Samitier, J., (2014). Large-scale dendrimer-based uneven nanopatterns for the study of local arginine-glycine-aspartic acid (RGD) density effects on cell adhesion Nano Research , 7, (3), 399-409

Cell adhesion processes are governed by the nanoscale arrangement of the extracellular matrix (ECM), being more affected by local rather than global concentrations of cell adhesive ligands. In many cell-based studies, grafting of dendrimers on surfaces has shown the benefits of the local increase in concentration provided by the dendritic configuration, although the lack of any reported surface characterization has limited any direct correlation between dendrimer disposition and cell response. In order to establish a proper correlation, some control over dendrimer surface deposition is desirable. Here, dendrimer nanopatterning has been employed to address arginine-glycine-aspartic acid (RGD) density effects on cell adhesion. Nanopatterned surfaces were fully characterized by atomic force microscopy (AFM), scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS), showing that tunable distributions of cell adhesive ligands on the surface are obtained as a function of the initial dendrimer bulk concentration. Cell experiments showed a clear correlation with dendrimer surface layout: Substrates presenting regions of high local ligand density resulted in a higher percentage of adhered cells and a higher degree of maturation of focal adhesions (FAs). Therefore, dendrimer nanopatterning is presented as a suitable and controlled approach to address the effect of local ligand density on cell response. Moreover, due to the easy modification of dendrimer peripheral groups, dendrimer nanopatterning can be further extended to other ECM ligands having density effects on cells.

JTD Keywords: Arginine-glycine-aspartic acid, Atomic force microscopy, Cell adhesion, Dendrimer, Focal adhesions, Scanning tunneling microscopy


Serra, T., Ortiz-Hernandez, M., Engel, E., Planell, J. A., Navarro, M., (2014). Relevance of PEG in PLA-based blends for tissue engineering 3D-printed scaffolds Materials Science and Engineering: C 38, (1), 55-62

Achieving high quality 3D-printed structures requires establishing the right printing conditions. Finding processing conditions that satisfy both the fabrication process and the final required scaffold properties is crucial. This work stresses the importance of studying the outcome of the plasticizing effect of PEG on PLA-based blends used for the fabrication of 3D-direct-printed scaffolds for tissue engineering applications. For this, PLA/PEG blends with 5, 10 and 20% (w/w) of PEG and PLA/PEG/bioactive CaP glass composites were processed in the form of 3D rapid prototyping scaffolds. Surface analysis and differential scanning calorimetry revealed a rearrangement of polymer chains and a topography, wettability and elastic modulus increase of the studied surfaces as PEG was incorporated. Moreover, addition of 10 and 20% PEG led to non-uniform 3D structures with lower mechanical properties. In vitro degradation studies showed that the inclusion of PEG significantly accelerated the degradation rate of the material. Results indicated that the presence of PEG not only improves PLA processing but also leads to relevant surface, geometrical and structural changes including modulation of the degradation rate of PLA-based 3D printed scaffolds.

JTD Keywords: 3D-printing, Polylactic acid, Rapid prototyping, Scaffold, Surface characterization


Álvarez, Zaida, Mateos-Timoneda, Miguel A., Hyrossová, Petra, Castaño, Oscar, Planell, Josep A., Perales, José C., Engel, Elisabeth, Alcántara, Soledad, (2013). The effect of the composition of PLA films and lactate release on glial and neuronal maturation and the maintenance of the neuronal progenitor niche Biomaterials 34, (9), 2221-2233

To develop tissue engineering strategies useful for repairing damage in the central nervous system (CNS) it is essential to design scaffolds that emulate the NSC niche and its tight control of neural cell genesis, growth, and differentiation. In this study we tested two types of poly l/dl lactic acid (PLA95/5 and PLA70/30), a biodegradable material permissive for neural cell adhesion and growth, as materials for nerve regeneration. Both PLA were slightly hydrophobic and negatively charged but differed in crystallinity, stiffness and degradation rate. PLA95/5 films were highly crystalline, stiff (GPa), and did not degrade significantly in the one-month period analyzed in culture. In contrast, PLA70/30 films were more amorphous, softer (MPa) and degraded faster, releasing significant amounts of lactate into the culture medium. PLA70/30 performs better than PLA95/5 for primary cortical neural cell adhesion, proliferation and differentiation, maintaining the pools of neuronal and glial progenitor cells in vitro. l-lactate in the medium recapitulated PLA70/30's maintenance of neuronal restricted progenitors but did not sustain bipotential or glial restricted progenitors in the cultures, as occurred when neural cells were grown on PLA70/30. Our results suggest that PLA70/30 may mimic some of the physical and biochemical characteristics of the NSC niche. Its mechanical and surface properties may act synergistically in the modulation of bipotential and glial restricted progenitor phenotypes, while it is l-lactate, either added to the medium or released by the film that drives the maintenance of neuronal restricted progenitor cell phenotypes.

JTD Keywords: Polylactic acid, Degradation, Neurons, Progenitors, Lactate, Glial cells, NSC niche


Serra, T., Planell, J. A., Navarro, M., (2013). High-resolution PLA-based composite scaffolds via 3-D printing technology Acta Biomaterialia 9, (3), 5521-5530

Fabrication of new biodegradable scaffolds that guide and stimulate tissue regeneration is still a major issue in tissue engineering approaches. Scaffolds that possess adequate biodegradability, pore size, interconnectivity, bioactivity and mechanical properties in accordance with the injured tissue are required. This work aimed to develop and characterize three-dimensional (3-D) scaffolds that fulfill the aforementioned requirements. For this, a nozzle-based rapid prototyping system was used to combine polylactic acid and a bioactive CaP glass to fabricate 3-D biodegradable scaffolds with two patterns (orthogonal and displaced double layer). Scanning electron microscopy and micro-computer tomography showed that 3-D scaffolds had completely interconnected porosity, uniform distribution of the glass particles, and a controlled and repetitive architecture. Surface properties were also assessed, showing that the incorporation of glass particles increased both the roughness and the hydrophilicity of the scaffolds. Mechanical tests indicated that compression strength is dependent on the scaffold geometry and the presence of glass. Preliminary cell response was studied with primary mesenchymal stem cells (MSC) and revealed that CaP glass improved cell adhesion. Overall, the results showed the suitability of the technique/materials combination to develop 3-D porous scaffolds and their initial biocompatibility, both being valuable characteristics for tissue engineering applications.

JTD Keywords: Rapid prototyping, Scaffold, Polylactic acid, Biodegradable, Composite


Levato, Riccardo, Mateos-Timoneda, Miguel A., Planell, Josep A., (2012). Preparation of biodegradable polylactide microparticles via a biocompatible procedure Macromolecular Bioscience 12, (4), 557-566

PLA MPs are prepared via a novel and toxic-chemical-free fabrication route using ethyl lactate, a green solvent and FDA-approved aroma. MPs are obtained by a solution jet break-up and solvent displacement method. Adjusting flow parameters allows the tuning of MPs size between 60 and 180 µm, with reduced polydispersity. Morphological analysis shows microporous particles with Janus-like surface. A fluorophore is successfully loaded into the MPs during their formation step. This versatile green solvent-based procedure is proven to be suitable for drug encapsulation and delivery applications. The method may be extended to different droplet generation techniques.

JTD Keywords: Biocompatibility, Biodegradable, Green solvents, Microparticles, Poly(lactic acid)


Acerbi, I., Luque, T., Giménez, A., Puig, M., Reguart, N., Farré, R., Navajas, D., Alcaraz, J., (2012). Integrin-specific mechanoresponses to compression and extension probed by cylindrical flat-ended afm tips in lung cells PLoS ONE 7, (2), e32261

Cells from lung and other tissues are subjected to forces of opposing directions that are largely transmitted through integrin-mediated adhesions. How cells respond to force bidirectionality remains ill defined. To address this question, we nanofabricated flat-ended cylindrical Atomic Force Microscopy (AFM) tips with ~1 μm 2 cross-section area. Tips were uncoated or coated with either integrin-specific (RGD) or non-specific (RGE/BSA) molecules, brought into contact with lung epithelial cells or fibroblasts for 30 s to form focal adhesion precursors, and used to probe cell resistance to deformation in compression and extension. We found that cell resistance to compression was globally higher than to extension regardless of the tip coating. In contrast, both tip-cell adhesion strength and resistance to compression and extension were the highest when probed at integrin-specific adhesions. These integrin-specific mechanoresponses required an intact actin cytoskeleton, and were dependent on tyrosine phosphatases and Ca 2+ signaling. Cell asymmetric mechanoresponse to compression and extension remained after 5 minutes of tip-cell adhesion, revealing that asymmetric resistance to force directionality is an intrinsic property of lung cells, as in most soft tissues. Our findings provide new insights on how lung cells probe the mechanochemical properties of the microenvironment, an important process for migration, repair and tissue homeostasis.

JTD Keywords: Arginylglycylaspartic acid, Arginylglycylglutamic acid, Bovine serum albumin, Calcium ion, Integrin, Protein tyrosine phosphatase, Unclassified drug


Serra, T., Navarro, M., Planell, J. A., (2012). Fabrication and characterization of biodegradable composite scaffolds for tissue engineering Innovative Developments in Virtual and Physical Prototyping 5th International Conference on Advanced Research and Rapid Prototyping (ed. Margarida, T., Ferreira, D.), Taylor & Francis (Leiria, Portugal) VR@P, 67-72

In this study, polylactic acid (PLA) and polyethylene glycol (PEG) were combined with soluble CaP glass particles and processed by rapid prototyping to obtain fully biodegradable structures for Tissue Engineering applications. The obtained 3D biodegradable structures were characterized in terms of their architecture and mechanical properties. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using Scanning Electron Microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. Well defined structures with pore size of 350-400μm (in the axial view), struts width of approximately 70-80μm, and a porosity ranging between 60-65% were obtained. The combination RP and PLA/PEG/CaP glass turned into promising fully degradable, mechanically stable, bioactive and biocompatible composite scaffolds for TE.

JTD Keywords: Axial view, Biodegradable composites, Composite scaffolds, Glass particles, Mechanically stable, Micro architectures, Micro computed tomography (micro-CT), Poly lactic acid, Scaffold morphology, Tissue engineering applications, Well-defined structures, Bioactive glass, Mechanical properties, Mechanical testing, Polyethylene glycols, Polymer blends, Rapid prototyping, Scaffolds (biology), Scanning electron microscopy, Computerized tomography


Ruiz, A., Mills, C. A., Valsesia, A., Martinez, E., Ceccone, G., Samitier, J., Colpo, P., Rossi, F., (2009). Large-area, nanoimprint-assisted microcontact stripping for the fabrication of microarrays of fouling/nonfouling nanostructures Small 5, (10), 1133-1137

Methods for the accurate positioning of nanometric beads on a substrate have been developed over a number of years, and range from serial atomic force microscopy (AFM)techniques for single-bead positioning to parallel techniques for the positioning of large populations of beads in monolayer or multilayer architectures, typically from a liquid suspension. For example, topographic cues have been used for bead-based protein array production, although in this case, there is a random distribution of beads within the topography. Bead patterning has also been achieved in capillaries using a micromolding in capillaries (MIMIC) technique. Line patterns with micrometer widths are possible with this technique, achieving good multilayer organization. For monolayer bead patterning at micrometer dimensions, electrostatic forces and similar electrostatic assemblies using nanoxerography, as well as patterning by selective chemical functionalization, by transfer of particles from a liquid–liquid interface, and by subtracting top–down processes, are possible.

JTD Keywords: Microcontact stripping, Nanostructures, Poly(acrylic acid), Polystyrene, Surface patterning


Merolli, A., Rocchi, L., Catalano, F., Planell, J., Engel, E., Martinez, E., Sbernardori, M. C., Marceddu, S., Leali, P. T., (2009). In vivo regeneration of rat sciatic nerve in a double-halved stitch-less guide: a pilot-study Microsurgery , 29, (4), 310-318

It is about 20 years that tubular nerve guides have been introduced into clinical practice as a reliable alternative to autograft, in gaps not-longer-than 20 mm, bringing the advantage of avoiding donor site sacrifice and morbidity. There are limitations in the application of tubular guides. First, tubular structure in itself makes surgical implantation difficult; second, stitch sutures required to secure the guide may represent a site of unfavorable fibroblastic reaction; third, maximum length and diameter of the guide correlate with the occurrence of a poorer central vascularization of regenerated nerve. We report on the in vivo testing of a new concept of nerve-guide (named NeuroBox) which is double-halved, not-degradable, rigid, and does not require any stitch to be held in place, employing acrylate glue instead. Five male Wistar rats had the new guide implanted in a 4-mm sciatic nerve defect; two guides incorporated a surface constituted of microtrenches aligned longitudinally. Further five rats had the 4-mm gap left without repair. Contralateral intact nerves were used as controls. After 2 months, nerve regeneration occurred in all animals treated by the NeuroBox; fine blood vessels were well represented. There was no regeneration in the un-treated animals. Even if the limited number of animals does not allow to draw definitive conclusions, some result can be highlighted: an easy surgical technique was associated with the box-shaped guide and acrylate glue was easily applied; an adequate intraneural vascularization was found concurrently with the regeneration of the nerve and no adverse fibroblastic proliferation was present.

JTD Keywords: Peripheral-nerve, Polyglycolic acid, Guidance cues, Collagen tube, Median nerve, Repair, Growth, Cyanoacrylate, Complications, Anastomosis


Navarro, M., Engel, E., Planell, J. A., Amaral, I., Barbosa, M., Ginebra, M. P., (2008). Surface characterization and cell response of a PLA/CaP glass biodegradable composite material Journal of Biomedical Materials Research - Part A , 85A, (2), 477-486

Bioabsorbable materials are of great interest for bone regeneration applications, since they are able to degrade gradually as new tissue is formed. In this work, a fully biodegradable composite material containing polylactic acid (PLA) and calcium phosphate (CaP) soluble glass particles has been characterized in terms of surface properties and cell response. Cell cultures were performed in direct contact with the materials and also with their extracts, and were evaluated using the MTT assay, alkaline phosphatase activity, and osteocalcin measurements. The CaP glass and PLA were used as reference materials. No significant differences were observed in cell proliferation with the extracts containing the degradation by-products of the three materials studied. A relation between the materials wettability and the material-cell interactions at the initial stages of contact was observed. The most hydrophilic material (CaP glass) presented the highest cell adhesion values as well as an earlier differentiation, followed by the PLA/glass material. The incorporation of glass particles into the PLA matrix increased surface roughness. SEM images showed that the heterogeneity of the composite material induced morphological changes in the cells cytoskeleton.

JTD Keywords: Glass, Polylactic acid, Surface analysis, Cell culture, In vitro test


Charles-Harris, M., Koch, M. A., Navarro, M., Lacroix, D., Engel, E., Planell, J. A., (2008). A PLA/calcium phosphate degradable composite material for bone tissue engineering: an in vitro study Journal of Materials Science-Materials in Medicine , 19, (4), 1503-1513

Biodegradable polymers reinforced with an inorganic phase such as calcium phosphate glasses may be a promising approach to fulfil the challenging requirements presented by 3D porous scaffolds for tissue engineering. Scaffolds' success depends mainly on their biological behaviour. This work is aimed to the in vitro study of polylactic acid (PLA)/CaP glass 3D porous constructs for bone regeneration. The scaffolds were elaborated using two different techniques, namely solvent-casting and phase-separation. The effect of scaffolds' micro and macrostructure on the biological response of these scaffolds was assayed. Cell proliferation, differentiation and morphology within the scaffolds were studied. Furthermore, polymer/glass scaffolds were seeded under dynamic conditions in a custom-made perfusion bioreactor. Results indicate that the final architecture of the solvent-cast or phase separated scaffolds have a significant effect on cells' behaviour. Solvent-cast scaffolds seem to be the best candidates for bone tissue engineering. Besides, dynamic seeding yielded a higher seeding efficiency in comparison with the static method.

JTD Keywords: Biocompatible Materials/ chemistry, Bone and Bones/ metabolism, Calcium Phosphates/ chemistry, Cell Differentiation, Cell Proliferation, Humans, Lactic Acid/ chemistry, Microscopy, Confocal, Microscopy, Electron, Scanning, Osteoblasts/metabolism, Permeability, Polymers/ chemistry, Porosity, Solvents/chemistry, Tissue Engineering/ methods