Engineering Immunomodulatory and Osteoinductive Implant Surfaces via Mussel Adhesion-Mediated Ion Coordination and Molecular Clicking

Abstract Immune action and new tissue formation are two distinct but overlapping stages involved in tissue regeneration process. However, current biomaterial design is trapped into a one-sided consideration with either focusing on the regulation of immune response or paying attention to induction of new tissue formation. Bone implants also face the same problem. In this work, we designed a dual-effect bone implant with immunomodulatory activity with direct osteogenicity by a mussel adhesion-mediated ion coordination and molecular clicking strategy. The mussel-inspired chemistry for surface adhesion, bioclickable way for molecular conjugation, and coordination means for ion loading led to an immunoactive Zn2+ ion and osteoinductive BMP-2 peptide co-modified coating on bone implants. We demonstrated that the dual-effect coating could better improve cytocompatibility and promote the polarization of macrophages to M2 phenotype in vitro and in vivo. Moreover, the Zn2+ ion and BMP-2 peptide co-modified bone implants showed optimal osteogenicity and osseointegration, thus improving implant stability in vivo. We anticipate this study would provide new ideas and solutions for engineering implants with immunoactivity and tissue inductivity to precisely adapt tissue regeneration microenvironment.