Tannic acid-mediated dual peptide-functionalized scaffolds to direct stem cell behavior and osteochondral regeneration

The development of cell-instructive scaffolds, which provide biochemical cues to direct endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior, has the potential to revolutionize osteochondral tissue engineering. However, scaffold material itself is generally lacking the inductive signals. Here, a novel peptide-functionalized scaffold was prepared by prime-coating Ca-alginate scaffold with tannic acid (TA) followed by conjugation of E7/P15 peptides (CA-TA-E7/P15). The system leveraged TA as a reactive intermediate between Ca-alginate and peptides due to the multiple functional groups of TA. These interactions induced by TA prime-coating contributed to enhanced scaffold stability and mechanical properties, increased peptide conjugation and sustained release of peptides without affecting their bioactivity, in a TA concentration-dependent manner. The conjugation of E7/P15 peptides endowed the scaffold with the potential to enhance BMSCs recruitment and deposition of cartilage and bone extracellular matrix (ECM). Furthermore, the prepared CA-TA-E7/P15 scaffold showed a promoted biological performance of simultaneous cartilage and subchondral bone regeneration in rabbit osteochondral defect model. These findings indicate that TA is an effective surface modification intermediate and crosslinking aid, and that the CA-TA-E7/P15 scaffold developed in this study serves as a promising cell-instructive scaffold for osteochondral regeneration.