Biomatériau

Un biomatériau (dit matériau biocompatible, à ne pas confondre avec les biomatériaux utilisés dans la construction, dit matériaux biosourcés) a été défini, selon la Société Européenne des Biomatériaux, comme « matériau conçu pour interagir avec les systèmes biologiques, qu'il participe à la constitution d'un dispositif à visée diagnostique ou à celle d'un substitut de tissu ou d'organe ou encore à celle d'un dispositif de suppléance (ou d'assistance) fonctionnelle » (Conférences de Chester (Royaume-Uni), 1986 et 1991). Il peut ainsi être considéré comme tout matériau utilisé pour remplacer une partie ou une fonction du corps de manière sure et fiable, acceptable d’un point de vue économique et physiologique. La science des biomatériaux est un domaine de la science des matériaux. Définition Le concept de biomatériaux étant polysémique, il en existe diverses définitions. Une définition souvent acceptée dans le domaine de la biologie et de la médecine est : : « Tout matéri

Gene delivery from responsive hyaluronic acid hydrogels for directed angiogenesis

Arnaud Felber

Tissue Engineering points to maintain, restore or to improve and create new tissues. This purpose typically involves the selection of a natural or synthetic biomaterial as a scaffold to create the biological substitutes. Furthermore, angiogenesis, the growth of new blood vessels from pre-existing ones, is a critical physiological process toward the success of tissue engineering. Along with this consideration, biomaterials that possess intrinsic angiogenic potential may be better candidates for tissue engineering. In the present report, we investigated the effects on the in vitro CAM assay (Folkman et al., A simple procedure for the long-term cultivation of chicken embryos, 1974; Auerbach et al., Angiogenesis assays: a critical overview, 2003) of hyaluronic acid (HA). HA derivatives were formed by reaction of the carboxylic acid groups of the soluble natural polymer with hydrazides, via carbodiimide-mediated coupling. This intermediate product was then further reacted with a cyclic thioimidate (Traut's reagent) compound for thiolation. We herein describe a physiologically compatible strategy to prepare HA hydrogels able to i) support drug delivery, and ii) support potential in situ encapsulation of cells. In this strategy, modified hyaluronic acid was cross-linked with itself and 6% (w:v) HA hydrogels were formed under physiological conditions by air oxidation of thiols to disulfides. According to a LIVE/DEAD assay, HA hydrogel showed to support cell growth and spreading. The biomaterial scaffold was loaded with plasmid and a DNA release assay was performed. However hydrogels swollen in proteases containing media indicated that only 10% of the integrated DNA remained inside after 48hours. The angiogenic properties of the hydrogel were investigated on the chicken chorioallantoic membrane assay. In addition, we also examined the involvement of plasmid Vascular Endothelial Growth Factor (VEGF) on the CAM by integrating the signal into the hydrogel. Angiogenesis was observed around the implanted biomaterial. In addition, fluorescence microscopy of perfused animal indicated the presence of blood vessels sprouting into the hydrogel matrices. We anticipate that this HA-based hydrogel is highly tunable (Shea et al., Non-viral vector delivery from PEG-hyaluronic acid hydrogels, 2007). In addition, hydrogels with this capability for localized delivery of gene therapy vectors and controllable stability have direct applications for tissue engineering and could be useful tool for several biomedical applications (Hubbell et al., Functional biomaterials design of novel biomaterials, 2001)

2008

Surface Grafted Polymer Brushes

Sorin Alexandru Ibanescu

Various strategies have been proposed and applied to prepare antibacterial materials able to respond to different requirements specific for antibacterial applications. Among diverse strategies the approach based on substrates modification with polymer brushes proved both versatile and reliable. Polymer brushes are thin polymeric films with all chains tethered with one end on a surface and since the development of SI-ATRP they can be obtained with good control over conformation, architecture and thickness. Therefore polymer brush coatings can be tailored with desired and fine tuned properties as functional biomaterials for a large variety of biomedical applications. The main objective of this Thesis was to develop versatile platforms for antibacterial applications based on polymer brush surfaces able to prevent bacteria adhesion and/or to kill bacteria on contact or through bacteria triggered controlled release of an antimicrobial compound. Moreover, novel systems based on polymer brushes have been synthesized as hydrolytically degradable platforms for potential biomedical applications. Chapter 1 analyses the mechanism of the biofilm formation and different strategies developed to inhibit bacterial adhesion, to prevent biofilm formation and proliferation and to reduce hospital-acquired bacterial infection. Various approaches for surfaces modification with polymer brushes are discussed, emphasizing on the possibilities of tailoring their antibacterial properties. Chapter 2 explores, for the first time, S. Epidermidis adhesion on PHEMA or POEGMA brushes on a wide range of grafting densities and film thicknesses. Both brushes carry functional groups on each repeating unit and are more appropriate for the development of platforms for novel biomedical applications. In Chapter 3 the possibility to obtain dual functional coatings combining the bacteria repellent character of the polymer brush with the possibility to selectively immobilize antibiotics is investigated. The antibacterial activity against S. Epidermidis of vancomycin modified surfaces is analyzed as a function of polymer brush structure and functional group used for coupling of the antibiotic. The aim of Chapter 4 is to develop systems based on polymer brush able to release an active compound in the presence of selected bacterial signals. A dye is coupled to PHEMA brushes via a specific linker sensitive to autolysins or beta-lactamase and its controlled release is monitored as a function of brush architecture. Finally, Chapter 5 focuses on improving existing hydrolytically degradable polymer brushes by neighboring group participation of a catalytic moiety. Moreover, the possibility to develop novel hydrolytically degradable polymer brushes based on polyphosphoesters is reported. The two studied systems are suitable as building blocks for platforms with antibacterial applications.

EPFL2015

Gene delivery from responsive hyaluronic acid hydrogels for directed angiogenesis

Arnaud Felber

2008

Surface Grafted Polymer Brushes

Sorin Alexandru Ibanescu

EPFL2015

Gene delivery from responsive hyaluronic acid hydrogels for directed angiogenesis

Chemical functionalization of ceramics biomaterials for the development of new bone implants

Surface Grafted Polymer Brushes

Gene delivery from responsive hyaluronic acid hydrogels for directed angiogenesis

Chemical functionalization of ceramics biomaterials for the development of new bone implants

Surface Grafted Polymer Brushes