Percutaneous devices play an essential role in patient care. However, the risks of infections associated with penetrating the skin are not inconsequential. Percutaneous devices are used for such diverse functions as dialysis, chemotherapy, attachments for prosthetic limbs and percutaneous sensors (glucose). Central venous catheters alone are associated with an estimated 80,000 to 250,000 blood stream infections annually, with an associated mortality of 12%-25% for each infection and a cost of >$28,000 per episode. The goal of this research is to create an interface that promotes epidermal and dermal cell integration with the surface of percutaneous medical devices. We believe that healing the cutaneous wound with cellular integration into percutaneous medical devices will provide a seal preventing bacterial attachment and subsequent biofilm formation. This innovation may prevent the most common cause of serious complications associated with these devices. Consistent with The NIH Roadmap, the proposed research will be conducted by an interdisciplinary research team including, skin biologists, researchers from two NSF Engineering Research Centers, one with expertise in advanced biomaterials, the other with expertise in the study of biofilm, as well as an industrial partner that develops and markets percutaneous devices for intravascular access. We will carry out the following Specific Aims: 1. Develop and characterize biomaterials that permit attachment of skin cells where percutaneous devices penetrate the skin. 2. Study the cellular and molecular events of the in vitro and in vivo skin responses (biointegration) to optimized biomaterials. 3. Evaluate bacterial attachment and biofilm formation as a function of skin/biomaterial integration.