Abstract
The immune responses are involved in every stage after implantation but the reported immune-regulated materials only work at the beginning without fully considering the different phases of bone healing. Here, poly(aryl-ether-ether-ketone) (PEEK) is coated with a programmed surface, which rapidly releases interleukin-10 (IL-10) in the first week and slowly delivers dexamethasone (DEX) up to 4 weeks. Owing to the synergistic effects of IL-10 and DEX, an aptly weak inflammation is triggered within the first week, followed by significant M2 polarization of macrophages and upregulation of the autophagy-related factors. The suitable immunomodulatory activities pave the way for osteogenesis and the steady release of DEX facilitates bone regeneration thereafter. The sequential immune-mediated process is also validated by an 8-week implementation on a rat model. This is the first attempt to construct implants by taking advantage of both immune-mediated modulation and sequential regulation spanning all bone regeneration phases, which provides insights into the fabrication of advanced biomaterials for tissue engineering and immunological therapeutics.