Engineering biomaterial interfaces to control foreign body response: Reducing giant cell formation and understanding host response to porous materials

All implanted devices and sensors are subject to the foreign body reaction, a cascade of events ultimately leading to chronic inflammation, device encapsulation, and impaired healing. We propose two approaches to alter the course of events and improve the fate of implants. First we show that osteopontin, a natural protein involved with bone homeostasis and wound healing, plays a role in regulation of foreign body giant cells. We are the first to show that absence of osteopontin increases macrophage fusion in response to biomaterial implants in vivo and the protein's ability to reduce foreign body giant cell formation in vitro. This suggests that presentation of this protein, either by surface immobilization or by controlled release, may reduce giant cell presence and the damage they induce to implants. Second we carefully study the effects of porosity on host response by analyzing in vivo phenotypic and genetic reactions to scaffolds possessing controlled, regular, highly interconnected pore structures. Previous studies have shown that at four weeks post-implantation, peak angiogenesis was observed in scaffolds with pore diameters around 35mum. We studied expression of genes at earlier timepoints which may contribute to the observed differences. Determination of genes key to angiogenesis at implant sites and their temporal profiles can aid rational design of future biomaterials and controlled release systems.