Moving forward materials-based regenerative medicine faces many challenges to ensure clinical success. Many of these challenges lie at the interface of molecular/structural biology and materials science. This review discusses this issue from a biological and material view-point, highlighting key biological processes and variables that can impact the repair processes. From a materials design stand point, developing materials that can promote healing over scarring is the key. All indicators suggest that polymeric materials are most well-suited for de novo engineering of tissues. In addition to biomolecular signals that are involved in controlling the fate of cells and neo-tissue morphogenesis at the site of implantation, this review also discusses recent advances in design of highly functional injectable biomaterials, that show promise in controlling local biological processes.