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

The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self-assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i-combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions. Using a range of microscopies and molecular simulations, the self-assembly of a library of combs in water is screened. It is discovered that the hydrophobic tails form the membrane's core and force the backbone into a rod conformation with nematic-like ordering confined to the interface with water. This particular organization resulted in membranes that combine the stability of classic polymersomes with the biomimetic thickness, flexibility, and lateral mobility of liposomes. Such unparalleled matching of biophysical properties and the ability to locally reconfigure the molecular topology of its constituents enable the harboring of functional components of natural membranes and fusion with living bacteria to “hijack” their periphery. This provides an almost inexhaustible palette to design the chemical and biological makeup of the i-combisomes membrane resulting in a powerful platform for fundamental studies and technological applications.

JTD Keywords: amphiphilic comb polymers, bottom-up synthetic biology, hybrid vesicles, polyelectrolyte-surfactant complexes, polymersomes, synthetic biomembranes, Amphiphilic comb polymers, Biomimetics, Bottom-up synthetic biology, Hybrid vesicles, Hydrophobic and hydrophilic interactions, Liposomes, Polyelectrolyte-surfactant complexes, Polymers, Polymersomes, Synthetic biomembranes, Vesicle fusion, Water

Quantum dots (QDs) are semiconductor nanoparticles with unique optical and electronic properties, whose interest as potential nano-theranostic platforms for imaging and sensing is increasing. The design and use of QDs requires the understanding of cell-nanoparticle interactions at a microscopic and nanoscale level. Model systems such as supported lipid bilayers (SLBs) are useful, less complex platforms mimicking physico-chemical properties of cell membranes. In this work, we investigated the effect of topographical homogeneity of SLBs bearing different surface charge in the adsorption of hydrophilic QDs. Using quartz-crystal microbalance, a label-free surface sensitive technique, we show significant differences in the interactions of QDs onto homogeneous and inhomogeneous SLBs formed following different strategies. Within short time scales, QDs adsorb onto topographically homogeneous, defect-free SLBs is driven by electrostatic interactions, leading to no layer disruption. After prolonged QD exposure, the nanomechanical stability of the SLB decreases suggesting nanoparticle insertion. In the case of inhomogeneous, defect containing layers, QDs target preferentially membrane defects, driven by a subtle interplay of electrostatic and entropic effects, inducing local vesicle rupture and QD insertion at membrane edges. © 2021

JTD Keywords: adsorption, atomic force microscopy, bilayer formation, gold nanoparticles, hydrophilic quantum dots, lipid membrane defects, model, nanomechanics, quartz crystal microbalance with dissipation, size, supported lipid bilayers, surfaces, Atomic force microscopy, Atomic-force-microscopy, Cell membrane, Cytology, Defect-free, Electronic properties, Electrostatics, Hydrophilic quantum dot, Hydrophilic quantum dots, Hydrophilicity, Hydrophilics, Hydrophobic and hydrophilic interactions, Lipid bilayers, Lipid membrane defect, Lipid membrane defects, Lipid membranes, Lipids, Nanocrystals, Nanomechanics, Optical and electronic properties, Quantum dots, Quartz, Quartz crystal microbalance techniques, Quartz crystal microbalance with dissipation, Quartz crystal microbalances, Quartz-crystal microbalance, Semiconductor nanoparticles, Semiconductor quantum dots, Supported lipid bilayers

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

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

Ubiquinone (UQ) is one of the main electron and proton shuttle molecules in biological systems, and dipalmitoylphosphatidylcholine (DPPC) is one of the most used model lipids. Supported planar bilayers (SPBs) are extensively accepted as biological model membranes. In this study, SPBs have been deposited on ITO, which is a semiconductor with good electrical and optical features. Specifically, topographic atomic force microscopy (AFM) images and force curves have been performed on SPBs with several DPPC:UQ ratios to study the location and the interaction of UQ in the SPB. Additionally, cyclic voltammetry has been used to understand the electrochemical behavior of DPPC:UQ SPBs. Obtained results show that, in our case, UQ is placed in two main different positions in SPBs. First, between the DPPC hydrophobic chains, fact that originates a decrease in the breakthrough force of the bilayer, and the second between the two leaflets that form the SPBs. This second position occurs when increasing the UQ content, fact that eventually forms UQ aggregates at high concentrations. The formation of aggregates produces an expansion of the SPB average height and a bimodal distribution of the breakthrough force. The voltammetric response of UQ depends on its position on the bilayer.

JTD Keywords: Bimodal distribution, Biological models, Dipalmitoyl phosphatidylcholine, Electrochemical behaviors, Hydrophobic chains, Supported lipid bilayers, Supported planar bilayers, Voltammetric response

Considering the structural role of type IV collagen (Col IV) in the assembly of the basement membrane (BM) and the perspective of mimicking its organization for vascular tissue engineering purposes, we studied the adsorption pattern of this protein on model hydrophilic (clean glass) and hydrophobic trichloro(octadecyl) silane (ODS) surfaces known to strongly affect the behavior of other matrix proteins. The amount of fluorescently labeled Col IV was quantified showing saturation of the surface for concentration of the adsorbing solution of about 50 mu g/ml, but with approximately twice more adsorbed protein on ODS. AFM studies revealed a fine-nearly single molecular size-network arrangement of Col IV on hydrophilic glass, which turns into a prominent and growing polygonal network consisting of molecular aggregates on hydrophobic ODS. The protein layer forms within minutes in a concentration-dependent manner. We further found that human umbilical vein endothelial cells (HUVEC) attach less efficiently to the aggregated Col IV (on ODS), as judged by the significantly altered cell spreading, focal adhesions formation and the development of actin cytoskeleton. Conversely, the immunofluorescence studies for integrins revealed that the fine Col IV network formed on hydrophilic substrata is better recognized by the cells via both alpha 1 and alpha 2 heterodimers which support cellular interaction, apart from these on hydrophobic ODS where almost no clustering of integrins was observed.

JTD Keywords: Collagen type IV, Adsorption, Assembly, Hydrophilic, Hydrophobic, Surfaces

Fibronectin (FN) fibrillogenesis is a cell-mediated process involving integrin activation that results in conformational changes of FN molecules and the organization of actin cytoskeleton. A similar process can be induced by some chemistries in the absence of cells, e.g., poly(ethyl acrylate) (PEA), which enhance FN-FN interactions leading to the formation of a biologically active network. Atomic force microscopy images of single FN molecules, at the early stages of adsorption on plane PEA, allow one to rationalize the process. Further, the role of the spatial organization of the FN network on the cellular response is investigated through its adsorption on electrospun fibers. Randomly oriented and aligned PEA fibers were prepared to mimic the three-dimensional organization of the extracellular matrix. The formation of the FN network on the PEA fibers but not on the supporting coverglass was confirmed. Fibroblasts aligned with oriented fibers, displayed extended morphology, developed linearly organized focal adhesion complexes, and matured actin filaments. Conversely, on random PEA fibers, cells acquired polygonal morphology with altered actin cytoskeleton but well-developed focal adhesions. Late FN matrix formation was also influenced: spatially organized FN matrix fibrils along the oriented PEA fibers and an altered arrangement on random ones.

JTD Keywords: AFM, Cell-adhesion, Dependent conformations, Hydrophobic surfaces, Extracellular-matrix, Bound fibronectin, Polymer surfaces, Integrin binding, Biocompatibility, Adsorption