Spatially and temporally regulated signaling between and within cell populations and the extracellular matrix govern tissue homeostasis, pathology and regeneration. Polymeric materials can mimic or enhance this communication and have the potential to intervene in these processes in a therapeutic manner. These cell instructive polymer systems provide insoluble cues (e.g., adhesion peptides) or soluble signaling molecules (e.g., growth factors). These material systems locally enable the activation, multiplication and differentiation of endogenous or exogenous cells. Multiple aspects of regeneration must be considered to design effective approaches to enable cell trafficking and ultimately elicit functional tissue repair. This issue has been addressed in the context of neovascularization.