Publications

Biomaterial-associated infections (BAIs) pose significant challenges in modern medical technologies, being a major postoperative complication and leading cause of implant failure. These infections significantly risk patient health, resulting in prolonged hospitalization, increased morbidity and mortality rates, and elevated treatment expenses. This comprehensive review examines the mechanisms driving bacterial adhesion and biofilm formation on biomaterial surfaces, offering an in-depth analysis of current antimicrobial strategies for preventing BAIs. We explore antimicrobial-eluting biomaterials, contact-killing surfaces, and antifouling coatings, emphasizing the application of antifouling polymer brushes on medical devices. Recent advancements in multifunctional antimicrobial biomaterials, which integrate multiple mechanisms for superior protection against BAIs, are also discussed. By evaluating the advantages and limitations of these strategies, this review aims to guide the design and development of highly efficient and biocompatible antimicrobial biomaterials. We highlight potential design routes that facilitate the transition from laboratory research to clinical applications. Additionally, we provide insights into the potential of synthetic biology as a novel approach to combat antimicrobial resistance. This review aspires to inspire future research and innovation, ultimately improving patient outcomes and advancing medical device technology.

JTD Keywords: Animals, Anti-bacterial agents, Antifouling coatings, Antimicrobial peptide, Antimicrobial-eluting coatings, Antimicrobial‐eluting coatings, Bacterial adhesion, Bacterial biofilm formation, Biocompatible materials, Biofilms, Biomaterial-associated infections, Biomaterial‐associated infections, Contact killing coatings, Humans, In-vitr, Infused porous surfaces, Metal-oxide surfaces, Multifunctional antimicrobial coating, Multifunctional antimicrobial coatings, Poly(l-lysine)-g-poly(ethylene glycol) layers, Polymer brushes, Prosthesis-related infections, Silicone oil, Superhydrophobic surfaces, Urinary catheters

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

Microbial biofilms are complex three-dimensional structures where sessile microbes are embedded in a polymeric extracellular matrix. Their resistance toward the host immune system as well as to a diverse range of antimicrobial treatments poses a serious health and development threat, being in the top 10 global public health threats declared by the World Health Organization. In an effort to combat biofilm-related microbial infections, several strategies have been developed to independently eliminate biofilms or to complement conventional antibiotic therapies. However, their limitations leave room for other treatment alternatives, where the application of nanotechnology to biofilm eradication has gained significant relevance in recent years. Their small size, penetration efficiency, and the design flexibility that they present makes them a promising alternative for biofilm infection treatment, although they also present set-backs. This review aims to describe the main possibilities and limitations of nanomedicine against biofilms, while covering the main aspects of biofilm formation and study, and the current therapies for biofilm treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

JTD Keywords: Anti-bacterial agents, Anti-infective agents, Antiinfective agent, Antimicrobial, Antimicrobials, Antimicrobials,bacteria,biofilm,infectious diseases,microorganism, Bacteria, Biofilm, Biofilm infections, Biofilms, Complex three dimensional structures, Diseases, Diverse range, Drug-delivery systems,in-vitro,cellular toxicity,nanoparticles,penetration,model,biocompatibility,perspectives,hyperthermia,diagnosi, Extracellular matrices, Global public health, Health risks, Infectious disease, Infectious diseases, Medical nanotechnology, Microbial biofilm, Microorganisms, Nanomedicine, Polymer, Polymers, Regulatory issues, Roadmap

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.

JTD Keywords: antimicrobial peptide, biomaterials, bone, coatings, performance, ph, resistance, silanization, silver nanoparticles, staphylococcus aureus, Anti-bacterial agents, Antimicrobial peptide, Coated materials, biocompatible, Metal nanoparticles, Reduces bacterial adhesion, Silanization, Silver, Silver nanoparticles, Staphylococcus aureus, Surface properties, Titanium, Titanium functionalization

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

Multiresponsive hydrogels, which are smart soft materials that respond to more than one external stimulus, have emerged as powerful tools for biomedical applications, such as drug delivery. Within this context and with the aim of eliminating the systematic administration of antibiotics, special attention is being paid to the development of systems for controlled delivery of antibiotic for topical treatment of bacterial infections. In this work, an electro-chemo responsive hydrogel able to release chloramphenicol (CAM), a broad spectrum antibiotic also used for anticancer therapy, is proposed. This has been prepared by grafting poly(acrylic acid) (PAA) to sodium alginate (Alg) and in situ encapsulation of poly(3,4-ethylenedioxythiophene) nanoparticles loaded with CAM (PEDOT/CAM NPs), which were obtained by emulsion polymerization. Although the response to electrical stimuli of PEDOT was the main control for the release of CAM from PEDOT/CAM NPs, the release by passive diffusion had a relatively important contribution. Conversely, the passive release of antibiotic from the whole engineered hydrogel system, Alg-g-PAA/PEDOT/CAM, was negligible, whereas significant release was achieved under electrostimulation in an acid environment. Bacterial tests and assays with cancer cells demonstrated that the biological activity of CAM remained after release by electrical stimulation. Notably, the successful dual-response of the developed hydrogel to electrical stimuli and pH changes evidence the great prospect of this smart material in the biomedical field, as a tool to fight against bacterial infections and to provide local cancer treatment.

JTD Keywords: drug-delivery, films, growth, nanoparticles, Anti-bacterial agents, Bacterial infections, Cancer stem-cells, Chloramphenicol, Humans, Hydrogels, Hydrogen-ion concentration

Since the discovery that nanostructured surfaces were able to kill bacteria, many works have been published focusing on the design of nanopatterned surfaces with antimicrobial properties. Synthetic bone grafts, based on calcium phosphate (CaP) formulations, can greatly benefit from this discovery if adequate nanotopographies can be developed. However, CaP are reactive materials and experience ionic exchanges when placed into aqueous solutions which may in turn affect cell behaviour and complicate the interpretation of the bactericidal results. The present study explores the bactericidal potential of two nanopillared CaP prepared by hydrolysis of two different sizes of alpha-tricalcium phosphate (alpha-TCP) powders under biomimetic or hydrothermal conditions. A more lethal bactericidal response toward Pseudomonas aeruginosa (similar to 75% killing efficiency of adhered bacteria) was obtained from the hydrothermally treated CaP which consisted in a more irregular topography in terms of pillar size (radius: 20-60 nm), interpillar distances (100-1500 nm) and pillar distribution (pillar groups forming bouquets) than the biomimetically treated one (radius: 20-40 nm and interpillar distances: 50-200 nm with a homogeneous pillar distribution). The material reactivity was greatly influenced by the type of medium (nutrient-rich versus nutrient-free) and the presence or not of bacteria. A lower reactivity and superior bacterial attachment were observed in the nutrient-free medium while a lower attachment was observed for the nutrient rich medium which was explained by a superior reactivity of the material paired with the lower tendency of planktonic bacteria to adhere on surfaces in the presence of nutrients. Importantly, the ionic exchanges produced by the presence of materials were not toxic to planktonic cells. Thus, we can conclude that topography was the main contributor to mortality in the bacterial adhesion tests.

JTD Keywords: bactericidal, calcium deficient hydroxyapatite, calcium phosphates, nanopillars, pseudomonas aeruginosa, reactivity, Adhesion, Anti-bacterial agents, Antibacterial, Bacterial adhesion, Bactericidal, Biomaterials, Biomimetics, Calcium deficient hydroxyapatite, Calcium phosphates, Hydroxyapatite, In-vitro, Infections, Nanopillars, Nanostructures, Pseudomonas aeruginosa, Pseudomonas-aeruginosa, Reactivity, Recent progress, Silver, Topography, Transmission

The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli. U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO3 and NH3, which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.

JTD Keywords: biofilms, carbonate, e. coli, enzymatic nanomotors, infections, lysozyme, micromotors, nanomachines, proteins, self-propulsion, Anti-bacterial agents, Biocatalysis, Biofilms, Canavalia, Drug carriers, E. coli, Eliminate escherichia-coli, Enzymatic nanomotors, Escherichia coli, Escherichia coli infections, Humans, Infections, Muramidase, Nanomachines, Nanoparticles, Self-propulsion, Silicon dioxide, Urease, Urinary tract infections