Perspectives on Synthetic Materials to Guide Tissue Regeneration for Osteochondral Defect Repair

Regenerative engineering holds the potential to treat clinically pervasive osteochondral defects (OCDs). In a synthetic materials-guided approach, the scaffold's chemical and physical properties alone instruct cellular behavior in order to effect regeneration, referred to herein as "instructive" properties. While this alleviates the costs and off-target risks associated with exogenous growth factors, the scaffold must be potently instructive to achieve tissue growth. Moreover, toward achieving functionality, such a scaffold should also recapitulate the spatial complexity of the osteochondral tissues. Thus, in addition to the regeneration of the articular cartilage and underlying cancellous bone, the complex osteochondral interface, composed of calcified cartilage and subchondral bone, should also be restored. In this Perspective, we highlight recent synthetic-based, instructive osteochondral scaffolds that have leveraged new material chemistries as well as innovative fabrication strategies. In particular, scaffolds with spatially complex chemical and morphological features have been prepared with electrospinning, solvent-casting-particulate-leaching, freeze-drying, and additive manufacturing. While few synthetic scaffolds have advanced to clinical studies to treat OCDs, these recent efforts point to the promising use of the chemical and physical properties of synthetic materials for regeneration of osteochondral tissues.