Biointerface engineering through amalgamation of gene technology and site‐specific growth factor conjugation for efficient osteodifferentiation

Abstract

The development of bone implants through bioinspired immobilization of growth factors remains a key issue in the generation of biological interfaces, especially in enhancing osteodifferentiation ability. In this study, we developed a strategy for surface functionalization of poly(lactide‐glycolide) (PLGA) and hydroxyapatite (HA) composite substrates through site‐specific conjugation of bone morphogenetic protein 2 containing 3,4‐hydroxyphenalyalanine (DOPA‐BMP2) mediated by tyrosinase and sortase A (SrtA). Firstly, the growth factor BMP2‐LPETG containing LPETG motif was successfully expressed in Escherichia coli through recombinant DNA technology. The excellent binding affinity of binding growth factor (DOPA‐BMP2) was achieved by converting the tyrosine residue (Y) of YKYKY‐GGG peptide into DOPA (X) by tyrosinase, which bound to the substrates. Then its GGG motif was specifically bound to the end of BMP2‐LPETG mediated by SrtA. Therefore, the generated bioactive DOPA‐BMP2/PLGA/HA substrates significantly promoted the osteogenic differentiation of MC3T3‐E1 cells. Thanks to this microbial‐assisted engineering approach, our work presents a facile and highly site‐specific strategy to engineer biomimetic materials for orthopedics and dentistry by effectively delivering growth factors, peptides, and other biomacromolecules.