A Synthetic Epitope‐Binding Receptor Enables In Situ Recruitment of Endogenous Bioactive Ligand for Tissue Regeneration

ABSTRACT In tissue engineering, tissue repair efficacy highly relies on the delivery of growth factor through scaffold biomaterials. However, the lack of controllability in use of these exogenous bioactive ligands raises significant ethical and safety concerns. In this context, we propose a ligand‐recruiting scaffold system for endogenous growth factor delivery, based on molecularly imprinted polymers (MIPs) featuring tailor‐made recognition toward target ligand. As a proof of concept, the osteogenic growth peptide (OGP), an endogenous growth factor for bone repair and regeneration, was selected as target ligand for MIPs design. The nonactive N‐terminal epitope of OGP (OGP 1‐9 ) was used as the template, and subsequently MIPs with tailor‐made recognition sites toward the OGP 1‐9 epitope was synthesized via a solid‐phase imprinting strategy. Due to specific epitope‐binding ability, the MIPs exhibited receptor‐like high affinity toward full‐length OGP while leaving its bioactive C‐terminal OGP 10‐14 exposed. Upon integration into scaffold biomaterial, the MIPs could enhance in situ osteogenic activity through epitope recognition‐mediated recruitment of endogenous OGP, thereby leading to improved bone tissue repair in vivo. This work demonstrates the potential of MIPs‐mediated ligand recognition for in situ recruitment of endogenous growth factors and provides new ideas for on‐demand design of growth factor‐free tissue engineering scaffolds.