Considerable effort has gone into developing in-dwelling therapeutic devices that depend on closed loop feedback control. In many cases, e.g. the artificial pancreas, a biosensor is needed to continuously monitor crucial physiological parameters. Although several studies have discussed biosensors which successfully functioned for several weeks in vivo, no sensor appears capable of reliably surviving long-term implantation, primarily owing to the deleterious consequences of wound healing and the foreign body response. This proposal test the hypothesis that easing the analyte transport limitations imposed by the wound healing process on implanted sensors will significantly improve biosensor performance in vivo. We will examine two factors associated with wound healing that limit biosensor access for blood borne analytes: (1) diffusion barriers imposed by sensor membrane biofouling and the densely fibrous capsular tissue that forms around implanted sensors, and (2) perfusion barriers imposed by the avascularity of the fibrous capsule. In pursuing this hypothesis, we intend to examine the efficacy of the following design modifications on in vivo biosensor performance: (1) incorporate textured angiogenic layer into the sensor packaging to disrupt formation of the fibrous capsule and promote neovascularization; (2) incorporate degradable polymers that release angiogenic factors into the textured angiogenic layer to further promote neovascularization; and (3) incorporate dialysis membranes (possibly with hydrogel modification) into the active sensing surface to minimize cellular deposition and protein absorption. The rt animal model will be used to test the influence of these modifications on the performance of long term implanted (i.e. 3-4 months) sensors. Finally, these modifications will be examined in functioning glucose biosensors developed in parallel with the biomaterials work.