Surface bisphosphonation of polyetheretherketone to manipulate immune response for advanced osseointegration.

[Display omitted] • Bisphosphonate groups are introduced onto PEEK implant using mussel-inspired chemistry. • Surface bisphosphonation mitigates the early acute inflammatory immune response by modulating macrophages M2 polarization. • A favorable osteoimmune microenvironment is constructed by surface bisphosphonation to enhance osteogenesis and angiogenesis. • PEEK implant with surface bisphosphonation achieves ameliorative osseointegration. Polyetheretherketone (PEEK) is deemed to be a promising alternative to biomedical metals for orthopedic and dental implantation attributed to its bone-like elastic modulus and good biocompatibility. Nevertheless, the bioinert PEEK elicits an acute and irreducible inflammatory immune response after implantation, resulting in fibrous encapsulation and ultimately inferior osseointegration. Therefore, endowing the PEEK surface with immunomodulatory function is essential for advanced osseointegration. Herein, surface bisphosphonation of PEEK is achieved by using mussel-inspired chemistry together with alendronate, which can not only mitigate the early servious inflammatory immune response by promoting macrophages polarization toward the pro-healing M2 phenotype, but also construct a favorable osteoimmune microenvironment to promote the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the osteogenesis of MC3T3-E1 osteoblasts. In vivo evaluation reveals an ameliorative osseointegration of PEEK implant after surface bisphosphonation, confirming the in vitro results. Our findings elucidate that the PEEK implant after surface bisphosphonation can positively regulate early immune reaction to facilitate subsequent angiogenesis and osteogenesis processes, which is desirable for orthopedic and dental implantation. [ABSTRACT FROM AUTHOR]