Click Functionalized, Tissue‐Specific Hydrogels for Osteochondral Tissue Engineering

Osteochondral repair requires the induction of both articular cartilage and subchondral bone development, necessitating the presentation of multiple tissue-specific cues for these highly distinct tissues. To provide a singular hydrogel system for the repair of either tissue type, we have developed biofunctionalized, mesenchymal stem cell-laden hydrogels that can present in situ biochemical cues for either chondrogenesis or osteogenesis by simple click modification of a crosslinker, poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT). After modifying PdBT with either cartilage-specific biomolecules (N-cadherin peptide, chondroitin sulfate) or bone-specific biomolecules (bone marrow homing peptide 1, glycine-histidine-lysine peptide), the biofunctionalized, PdBT-crosslinked hydrogels can selectively promote the desired bone- or cartilage-like matrix synthesis and tissue-specific gene expression, with effects dependent on both biomolecule selection and concentration. Our findings establish the versatility of this click functionalized hydrogel system as well as its ability to promote in vitro development of osteochondral tissue phenotypes.