Mussel-inspired alkaline phosphatase-specific coating on orthopedic implants for spatiotemporal modulating local osteoimmune microenvironment to facilitate osseointegration

Inadequate initial osseointegration and consequent prosthesis loosening are the most severe complications after artificial arthroplasty. Proper immune responses are crucial for the successful implantation of artificial pros-theses. Macrophages are central in osteoimmunomodulation because they exert distinct functions with highly plasticity. Herein, we developed an alkaline phosphatase (ALP) sensitive mussel-inspired coating on orthopedic implants for promoting osseointegration. First, the resveratrol-alendronate complexes were deposited on tita-nium implant surface through mussel-inspired interfacial interactions. Upon prosthesis implantation, macro-phages first polarized towards M1 type to initiate inflammatory responses and bone regeneration. As osteogenesis progresses, increasing amounts of ALP secreted by osteoblasts was cleaved the resveratrol-alendronate complexes. Then, the released resveratrol further promoted osteogenic differentiation of BMSCs and induced locoregional macrophages M2 polarization. Our results demonstrated that the bioinspired osteoimmunomodulation coating remarkably facilitated the prosthesis-bone integration by spatiotemporally modulating macrophages switching from M1 to M2 polarization in response to a real-time healing signal during osteogenesis. In summary, the mussel-inspired osteoimmunomodulation coating technology may provide a new approach for promoting osseointegration after artificial arthroplasty.