Investigation of recombinant human elastin polypeptides as non-thrombogenic coatings (original) (raw)
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Biomaterials, 2007
The ability of a cellular construct to guide and promote tissue repair strongly relies on three components, namely, cell, scaffold and growth factors. We aimed to investigate the osteopromotive properties of cellular constructs composed of poly-e-caprolactone (PCL) and rabbit bone marrow stromal cells (BMSCs), or BMSCs engineered to express bone morphogenetic protein 4 (BMP4). Highly porous biodegradable PCL scaffolds were obtained via phase inversion/salt leaching technique. BMSCs and transfected BMSCs were seeded within the scaffolds by using an alternate flow perfusion system and implanted into non-critical size defects in New Zealand rabbit femurs. In vivo biocompatibility, osteogenic and angiogenic effects induced by the presence of scaffolds were assessed by histology and histomorphometry of the femurs, retrieved 4 and 8 weeks after surgery. PCL without cells showed scarce bone formation at the scaffold-bone interface (29% bone/implant contact and 62% fibrous tissue/implant contact) and scarce PCL resorption (16%). Conversely, PCL seeded with autologous BMSCs stimulated new tissue formation into the macropores of the implant (20%) and neotissue vascularization. Finally, the BMP4-expressing BMSCs strongly favoured osteoinductivity of cellular constructs, as demonstrated by a more extensive bone/scaffold contact. r
Biomaterials, 2005
The polymer poly-N-acetylglucosamine (pGlcNAc) containing fiber material is becoming increasingly important as a topical agent for hemostasis at wound sites. The pGlcNAc polymeric fiber provides hemostasis through redundant mechanisms that include platelet activation for fibrin network formation. The research presented here better defines the mechanism for the effect of pGlcNAc containing fibers on platelet-mediated processes. Adsorption experiments demonstrated that pGlcNAc fibers tightly bind most major plasma proteins and a specific sub-set of platelet surface proteins, including the integrin b 3 subunit (CD61) and the von Willebrand receptor GP1b (CD42b). The result of this interaction is a platelet-dependent acceleration of fibrin gel formation. Accelerated fibrin polymerization is sensitive to factor XII inhibition by corn trypsin inhibitor and integrin inactivation with integrilin. Confocal microscopy studies show that when platelet integrins contact plasma protein-saturated pGlcNAc fibers, an increase in intracellular free calcium for platelet activation occurs to drive surface expression of phosphatidyl serine (PS). Thus, a catalytic surface for thrombin generation and accelerated fibrin clot formation results from the interaction of platelets with pGlcNAc. These findings, when considered with the observation that pGlcNAc fibers also induce red blood cell agglutination and vasoconstriction, provides an explanation for the ability of the pGlcNAc material to provide hemostasis in a wide variety of clinical applications. r
Biomolecular surface coating to enhance orthopaedic tissue healing and integration
Biomaterials, 2007
Implant osseointegration is a prerequisite for clinical success in orthopaedic and dental applications, many of which are restricted by loosening. Biomaterial surface modification approaches, including calcium-phosphate ceramic coatings and macro/microporosity, have had limited success in promoting integration. To improve osseointegration, titanium surfaces were coated with the glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) collagen-mimetic peptide, selectively promoting a 2 b 1 integrin binding, a crucial event for osteoblastic differentiation. Titanium surfaces presenting GFOGER triggered osteoblastic differentiation and mineral deposition in bone marrow stromal cells, leading to enhanced osteoblastic function compared to unmodified titanium. Furthermore, this integrin-targeted coating significantly improved in vivo peri-implant bone regeneration and osseointegration, as characterized by bone-implant contact and mechanical fixation, compared to untreated titanium in a rat cortical bone-implant model. GFOGERmodified implants also significantly enhanced osseointegration compared to surfaces modified with full-length type I collagen, highlighting the importance of presenting specific biofunctional domains within the native ligand. In addition, this biomimetic implant coating is generated using a simple, single-step procedure that readily translates to a clinical environment with minimal processing and cytotoxicity concerns. Therefore, this study establishes a biologically active and clinically relevant implant-coating strategy that enhances bone repair and orthopaedic implant integration. r
Structural requirements for stabilization of vascular elastin by polyphenolic tannins
Biomaterials, 2006
Elastin-associated degeneration and calcification are potential causes of long-term failure of glutaraldehyde (Glut) fixed tissue bioprostheses used in cardiovascular surgery. This vulnerability may be attributed to the inability of Glut to cross-link and adequately protect vascular elastin from enzymatic attack. Tannic acid (TA), a poly galloyl glucose (Glc), is compatible with Glut fixation, binds to vascular elastin, improves resistance to degradation and reduces in vivo calcification. While these results provided evidence of a beneficial interaction between elastin and TA, the nature and mechanisms of these interactions are unclear; moreover, TA-elastin binding exhibits a partial instability after long-term interaction with vascular elastin which could contribute to issues of implant toxicity. In present studies, we used resistance to elastase, mechanical properties, and cell viability assays to evaluate the elastin-stabilizing potential and cytotoxicity of TA derivatives and individual TA components such as acetylated TA (AcTA), pentagalloylglucose (PGG), free gallic acid (Gall) and Glc. Our comparative study demonstrates that polyphenolic hydroxyl groups are the main structural groups essential to the interaction between TA and elastin. Furthermore, we show that PGG, the core structure of TA, possesses the same unique elastinstabilizing qualities of TA, yet it is much less cytotoxic than TA and thus could be potentially useful as an elastin-stabilizing agent for cardiovascular bioprostheses. r
Acta Biomaterialia, 2015
We explored the use of recently developed gels obtained by the catalyst free click reaction of elastin-like recombinamers (ELRs) to fabricate a new class of covered stents. The approach consists in embedding bare metal stents in the ELR gels by injection molding, followed by endothelialization under dynamic pressure and flow conditions in a bioreactor. The mechanical properties of the gels could be easily tuned by choosing the adequate concentration of the ELR components and their biofunctionality could be tailored by inserting specific sequences (RGD and REDV). The ELR-covered stents exhibited mechanical stability under high flow conditions and could undergo crimping and deployment without damage. The presence of RGD in the ELR used to cover the stent supported full endothelialization in less than 2 weeks in vitro. Minimal platelet adhesion and fibrin adsorption were detected after exposure to blood, as shown by immunostaining and scanning electron microscopy. These results prove the potential of this approach towards a new and more effective generation of covered stents which exclude the atherosclerotic plaque from the blood stream and have high biocompatibility, physiological hemocompatibility and reduced response of the immune system.
Polymers
Coronary heart disease remains one of the leading causes of death in most countries. Healthcare improvements have seen a shift in the presentation of disease with a reducing number of ST-segment elevation myocardial infarctions (STEMIs), largely due to earlier reperfusion strategies such as percutaneous coronary intervention (PCI). Stents have revolutionized the care of these patients, but the long-term effects of these devices have been brought to the fore. The conceptual and technologic evolution of these devices from bare-metal stents led to the creation and wide application of drug-eluting stents; further research introduced the idea of polymer-based resorbable stents. We look at the evolution of stents and the multiple advantages and disadvantages offered by each of the different polymers used to make stents in order to identify what the stent of the future may consist of whilst highlighting properties that are beneficial to the patient alongside the role of the surgeon, the ca...
Scientific Reports, 2017
Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-codiethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve reendothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissueengineered vascular grafts for cardiovascular therapies with small caliber vessels.