Coatings For Implantable Devices Research Articles

Recent advances in self-assembling peptide matrices as functional coatings for implantable devices.

Nature has evolved numerous supramolecular machineries for modulating various cellular functions. Inspired by the assembly of these sophisticated structures in nature, the controlled assembly of synthetic peptides emerges as a promising approach to therapeutically relevant applications. The self-assembling biomimetic peptides could form well-ordered architectures through non-covalent interactions such as π-π stacking, van der Waals, electrostatic, and hydrogen bonding. In addition, the peptidic building blocks are highly biocompatible and allow facile chemical manipulation with diverse functionalities. For decades, a serious of engineered self-assembling peptides have been extensively studied as functional hydrogels for various applications. Meanwhile, the surface modification strategies based on self-assembling peptide matrices have also raised the attention of biomaterials researchers due to their programmability and 3D porous morphologies. This concise review will cover recent advances in self-assembling peptide matrices as functional coatings for implantable devices. The opportunities and challenges in this field will also be discussed.

Evolutionary design of optimal surface topographies for biomaterials

Natural evolution tackles optimization by producing many genetic variants and exposing these variants to selective pressure, resulting in the survival of the fittest. We use high throughput screening of large libraries of materials with differing surface topographies to probe the interactions of implantable device coatings with cells and tissues. However, the vast size of possible parameter design space precludes a brute force approach to screening all topographical possibilities. Here, we took inspiration from Nature to optimize materials surface topographies using evolutionary algorithms. We show that successive cycles of material design, production, fitness assessment, selection, and mutation results in optimization of biomaterials designs. Starting from a small selection of topographically designed surfaces that upregulate expression of an osteogenic marker, we used genetic crossover and random mutagenesis to generate new generations of topographies.

An eco-friendly synthesis, characterisation and antibacterial applications of gellan gum based silver nanocomposite hydrogel

Gellan gum based silver nanocomposite hydrogel prepared by using microwave assisted method. The mixture of Gellan gum, acrylamide, and 2-Acrylamido methyl propane sulphonic acid in presence of Ammonium persulphate as a intiator, and N,N-methylenebisacrylamide as cross linker resulted in the cross linked graft copolymer network (GG-g-poly(AAm-co-AMPS)). Silver nano particles have been formed and stabilized by using trisodium citrate in the gel network to reduce silver nitrate. The hydrogel and nanocomposite were characterized using X-ray diffraction method (XRD), transmission electron microscopy (TEM) and UV-Vis spectroscopy techniques. UV-Vis spectroscopy confirmed the presence Ag NPs in the hydrogels due the characteristic plasmon resonance surface. Further XRD analysis also confirms the presence of Ag NPs. The effect of incorporation of Ag NPs on the biological activity of GG-g-poly (AAm-co-AMPS) gel was studied by zone inhibition method considering two bacterial strains. The composite gel exhibited higher antibacterial activity compared to the parent gel. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections

Oscillating of physicochemical and biological properties of metal particles on their sonochemical treatment.

Different metal particles are increasingly used to target bacteria as an alternative to antibiotics. Despite numerous data about treating bacterial infections, the utilization of metal particles in antibacterial coatings for implantable devices and medicinal materials promoting wound healing. The antibacterial mechanisms of nanoscale and microscale particles are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. Thus, investigation of the antibacterial mechanisms of nanostructured metal particles is very important for the development of more effective antimicrobial materials. However, it is very difficult to develop a proper model for revealing the antibacterial mechanisms due to difficulty to choose a method that allows obtaining materials of various properties under approximately the same conditions. In this paper, we propose a green and feasible technique to create critical conditions for modification of zinc particles at highly non-equilibrium states. We demonstrate that the sonication process can be useful for fabrication the materials with oscillating physical, chemical and antibacterial properties. We believe this method besides medical applications can be also used in natural science basic research as an experimental tool for modelling the physical and chemical processes. After the sonication, the zinc particles exhibit a different surface morphology and amount of leached Zn2+ ions compared to initial ones. It has been revealed that oscillations of the Zn2+ ions concentration lead to oscillation the antibacterial properties. Thus, the properties of the materials can be easily altered by adjusting the ultrasound energy dissipated via varying the sonication.

Lysozyme sorption by pure-silica zeolite MFI films

Nanostructured, porous materials, like zeolites, have been suggested as possible materials for biomedical applications in implantable device coatings, tissue engineering, and drug delivery systems due to their unique interactions with biomolecules and biological environments. Here, the fundamental sorption interactions between a pure-silica zeolite (MFI) with lysozyme, a positively charged enzyme, are discussed. Lysozyme sorption is considered a model for innate immunological processes in the body; high lysozyme sorption has been correlated with materials that are naturally antibiotic and act as cell guardians. The impact of three different parameters on the sorption of lysozyme was evaluated via enzyme-linked immunosorbent assays (ELISAs) and bicinchoninic acid assays (BCA assays), including the orientation of the film’s crystal structure (b-oriented or randomly-oriented), the lysozyme incubation volume (200 μL, 400 μL, 600 μL, 800 μL), and the lysozyme incubation time (1, 6, and 24 h). Additionally, the films were characterized via X-ray diffraction, scanning electron microscopy, and energy dispersive spectroscopy. In this work, we demonstrated that MFI films are capable of lysozyme sorption. Further, our observations suggested that, while crystal orientation did not play a significant role in the sorption process, incubation volume and time both impact sorption. The highest amounts of sorbed lysozyme were detected when films were incubated at intermediate volumes (400 and 600 μL) and shorter incubation times. The films’ ability to sorb differing amounts of lysozyme, depending on uptake parameters, make MFI films and coatings tailorable candidates for supports and/or coatings for implantable devices.

Electroactive Mg2+-Hydroxyapatite Nanostructured Networks against Drug-Resistant Bone Infection Strains.

Surface colonization competition between bacteria and host cells is one of the critical factors involved in tissue/implant integration. Current biomaterials are evaluated for their ability both of withstanding favorable responses of host tissue cells and of resisting bacterial contamination. In this work, the antibacterial ability of biocompatible Mg2+-substituted nanostructured hydroxyapatite (HA) was investigated. The densities of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli strains were significantly decreased after culture in the presence of Mg-substituted HA materials in direct correlation with Mg2+-Ca2+ switch in the HA lattice. It was noticed that this decrease was accompanied by a minimal alteration of bacterial environments; therefore, the Mg2+-HA antibacterial effect was associated with the material surface topography and it electroactive behavior. It was observed that 2.23 wt % Mg2+-HA samples exhibited the best antibacterial performance; it decreased 2-fold the initial population of E. coli, P. aeruginosa, and S. aureus at the intermediate concentration (50 mg mL-1 of broth). Our results reinforce the potential of Mg-HA nanostructured materials to be used in antibacterial coatings for implantable devices and/or medicinal materials to prevent bone infection and to promote wound healing.

The antimicrobial activity of nanoparticles: present situation and prospects for the future.

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.

Robust mechanical property measurements of fibrous parylene-C thin-film substrate via moiré contouring technology

Parylene-C is a bio-inert, bio-compatible and relatively inexpensive material with many bio-medical applications from coatings for implantable devices to bio-scaffolds. The main objective of this research was to demonstrate a novel approach to accurately measure the mechanical properties of free-standing fibrous thin-film substrates (TFS) of parylene-C. For that purpose, a two-stage experimental protocol based on the use of moiré contouring technology was developed. In this protocol, local measurements employing an advanced moiré setup that uses non-conventional illumination (i.e. evanescent field) are first performed to gather high-resolution information on a small region of the specimen; then, global measurements based on shadow moiré are performed to monitor the overall behavior of the membrane. The protocol was first calibrated for an aluminum foil and then partially applied to the fibrous parylene-C TFS. Material properties extracted from experiments are f0ully consistent with the data reported in literature and the results of a hybrid identification procedure based on the combination of finite element analysis and nonlinear optimization. The results will help lay the foundation for developing a comprehensive understanding of the influence that morphology and stresses play in the ability to enhance and sustain cell growth and tissue development, for biomedical applications.

Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.

Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: (1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or (2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and that of diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.

Novel thromboresistant materials

The development of a clinically durable small-diameter vascular graft as well as permanently implantable biosensors and artificial organ systems that interface with blood, including the artificial heart, kidney, liver, and lung, remain limited by surface-induced thrombotic responses. Recent breakthroughs in materials science, along with a growing understanding of the molecular events that underlay thrombosis, has led to the design and clinical evaluation of a variety of biologically active coatings that inhibit components of the coagulation pathway and platelet responses by surface immobilization or controlled release of bioactive agents. This report reviews recent progress in generating synthetic thromboresistant surfaces that inhibit (1) protein and cell adsorption, (2) thrombin and fibrin formation, and (3) platelet activation and aggregation.

Preparation of a novel freeze thawed poly(vinyl alcohol) composite hydrogel for drug delivery applications

We describe a drug delivery system based on a physically cross-linked poly(vinyl alcohol) (PVA) hydrogel for the release of Theophylline (TH). A composite was created by freezing an aqueous solution of PVA/NaOH onto a PVA/poly(acrylic acid) substrate. This formed a strong interface and demonstrated greater physical strength than the hydrogel alone. Such systems have potential for a variety of localised controlled drug delivery applications, for example, as coatings for implantable devices. Importantly, the results suggest that a versatile synthetic platform is possible that may provide different functional materials or combination of such. The resultant samples were characterised using optical microscopy, modulated differential scanning calorimetry (MDSC) and dissolution testing. The microstructure of the gels was examined using micro-thermal analysis (μTA) which is a combination of atomic force microscopy and thermal analysis. TH was found to have an effect on the crystalline structure and dissolution showed a Fickian release, suggesting that swelling and crystallinity were the controlling mechanisms.

In vivo biocompatibility and stability of a substrate-supported polymerizable membrane-mimetic film

The cell membrane establishes an important paradigm for the molecular engineering of coatings for implantable devices because of its intrinsic biocompatibility and ability to act as a template for the assembly of diverse membrane-associated macromolecules. A stabilized membrane-mimetic film was assembled on alginate/Ca(2+) hydrogel microcapsules by in situ polymerization of an acrylate functionalized phospholipid. The phospholipid monomer was prepared as unilamellar vesicles and fused onto octadecyl chains that were components of an amphiphilic terpolymer anchored onto a polyelectrolyte multilayer (PEM) by electrostatic interactions. Microcapsules coated with a membrane-mimetic film were implanted into the peritoneal cavity of C57BL/6 mice, and the short-term biostability and biocompatibility of membrane-mimetic films assembled on two different alginate/poly(l-lysine) PEM cushions were compared. The nature of the underlying PEM support had a profound impact on the biocompatibility of the membrane-mimetic film, as the percentage of retrieved microcapsules completely overgrown with host cells shifted from 66+/-5.9% to less than 1% when modifications to the PEM were made. When assembled on the appropriate PEM support, biocompatibility of membrane-mimetic-coated microspheres was high wherein 87.5+/-5.7% of the implanted microspheres were retrieved 4 weeks after implantation and 92.6+/-6.4% of the retrieved capsules were free of cell adhesion or fibrotic overgrowth. Finally, 4 weeks after implantation, microspheres coated with a Texas red-labeled membrane-mimetic film were imaged with confocal microscopy and exhibited a uniform film around the periphery of the implant, indicating a high degree of film biostability. Hence, membrane-mimetic films provide a new route for generating robust, biocompatible, and biochemically heterogeneous coatings for implantable devices through molecular self-assembly.

A Molecular Dynamics Study of the Physical Basis of Stability of Polypeptide Multilayer Nanofilms

Electrostatic layer-by-layer assembly (LBL) is a versatile method of fabricating ultrathin multilayer films, coatings, and microcapsules from materials in solution, notably, oppositely charged polyelectrolytes in water. Polypeptides, a special type of polyelectrolyte, have recently shown promise for a range of applications in biotechnology and medicine, for example, artificial cells, drug delivery systems, cell/tissue scaffolds, artificial viruses, and implantable device coatings. Poly(L-lysine) (PLL) and poly(L-glutamic acid) (PLGA) at neutral pH are model oppositely charged polypeptides. Experimental studies have shown that PLL/PLGA multilayer films contain a substantial amount of beta-sheets. Here, we present findings of a molecular dynamics (MD) study of the physical basis of interaction between PLL and PLGA in multilayer film models. Simulations have been carried out to study structural and dynamical properties of PLL/PLGA aggregates in beta-sheet conformation. The results suggest that hydrophobic interactions, in addition to electrostatics interactions, play a significant role in PLL/PLGA multilayers. The preferred orientation of peptides in the beta-sheet structures is antiparallel within sheets and parallel between sheets. Intersheet hydrogen-bond formation is more likely the result of peptide association than the cause. The approach provides a general means to understand better how various types of noncovalent interactions contribute to the structure and stability of polypeptide multilayer films.

Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels

The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.