A primary challenge in implantable biomaterials is the host response at the tissue-material interface. Protein adsorption, immune activation, and fibrotic encapsulation gradually isolate implants from surrounding tissues and restrict transport, often leading to failure of both drug-delivery devices and cell therapies. In this talk, I will describe our work using zwitterionic polymer materials to engineer this interface and how it improves tissue compatibility and functional integration of implanted systems in the subcutaneous space. I will present results showing enhanced durability and performance of both encapsulated islet grafts and insulin-delivery catheters. I will also discuss mechanistic studies on how zwitterionic interfaces influence inflammatory and fibrotic pathways while preserving molecular transport. Finally, I will briefly introduce zwitterionic formulations developed for anti-adhesion applications.