We are seeking to augment rotator cuff repair and peripheral nerve regeneration by developing biomimetic scaffolds capable of recapitulating the compositional, structural, mechanical, and cellular features of the native tissues. Rotator cuff tears are prevalent in the elderly population. Unfortunately, successful repair remains a major clinical challenge, with high post-operative failure rates. At the root of these failures is the poor healing at the repaired tendon-to-bone insertion, and the lack of regeneration of the native attachment structure. We are developing biomimetic scaffolds to augment the surgical repair and healing of the tendon-to-bone attachment. The research is built around the premise that scaffolds can be designed with hierarchical, functionally-graded structures to match the native enthesis for the regeneration of a robust interface between the reattached tendon and bone. When combined with mesenchymal stem cells, the translational potential of the scaffolds in enhancing the formation of a mechanically functional tendon-to-bone insertion are tested in a clinically relevant rotator cuff injury-and-repair model. Peripheral nerve injury is a large-scale problem that annually affects more than one million people in the US. We are developing nerve guidance conduits based on electrospun fibers for the surgical repair of large defects in thick nerves. The conduit facilitates nerve regeneration across a gap by providing a protective environment, limiting the possible directions of axonal sprouting, concentrating neurotrophic factors, and offering physical guidance to neurite extension. Specifically, we are working with conduits featuring a multi-tubular design to recapitulate the fascicles typical of a peripheral nerve while providing good mechanical strength to resist kinking and distortion during surgery. We augment nerve regeneration by leveraging the physical cue arising from the uniaxial alignment of electrospun fibers and nanoscale grooves engraved in the surface of the fibers, in addition to the biological cues provided by Schwann cells and/or encapsulated neurotrophic factors. A combination of in vitro and in vivo models are used to optimize the design and parameters of the conduits for peripheral nerve repair and functional recovery.