Porous hydrogels with well-defined pore structure for biomaterials applications.

摘要

When any medical device is implanted inside the body, the natural inflammatory response causes the device to be encapsulated with a thin layer of dense, relatively avascular fibrous tissue, effectively sealing off the device from the surrounding tissue and isolating it from the rest of the body. For medical devices such as electrodes and glucose sensors, where functionality depends on the ability of the device to interact with the surrounding biochemistry, the "foreign body response" poses a formidable obstacle.; Previous studies have demonstrated that porous materials with pore dimensions on the order of cell dimensions can induce a modified foreign body response, resulting in more vascularized capsule tissue. However, the utility of these studies is limited because the materials used had broad pore size distributions and poorly defined pore geometries. This thesis is motivated by the unavailability of biomaterials with well-defined and controlled pore size, and by the lack of understanding of the relationships between pore dimensions and the foreign body response.; Our sphere templating technology permits the fabrication of open-pore structures with precisely controlled pore dimensions. We can produce these sphere-templated pore structures out of a variety of polymeric materials, including poly(2-hydroxyethyl methacrylate) (polyHEMA), silicone rubber, and degradable copolymers of polyHEMA and poly(epsilon-caprolactone).; We applied our precision-engineered pore structures in vivo to investigate the role of pore size in the foreign body response. We implanted porous polyHEMA with various pore geometries under the skin of mice and found that the level of intra-pore vascularization increases with decreasing pore size, with vascular density directly proportional to the specific surface area of the implant, and that the threshold pore throat diameter for rapid tissue in-growth is approximately 8 mum. Based on our empirical results coupled with first principles, we developed a model for the prediction of intra-implant vascular density as a function of pore dimensions. These findings, which constitute a major advance in the understanding of the relationships between pore geometry and the foreign body response, have important implications for the design of tissue-biomaterial interfaces and other applications where control of vascular architecture is critical to function.