Switching On and Off Macrophages by a “Bridge‐Burning” Coating Improves Bone‐Implant Integration under Osteoporosis

Abstract Osteoporosis poses substantial challenges for biomaterials implantation. New approaches to improve bone‐implant integration should resolve the fundamental dilemma of inflammation—proper inflammation is required at early stages but should be suppressed later for better healing, especially under osteoporosis. However, precisely switching on and off inflammation around implants in vivo remains unachieved. To address this challenge, a “bridge‐burning” coating material that comprises a macrophage‐activating glycan covalently crosslinked by a macrophage‐eliminating bisphosphonate to titanium implant surface is designed. Upon implantation, the glycan instructs host macrophages to release pro‐osteogenic cytokines (“switch‐on”), promoting bone cell differentiation. Later, increasingly mature bone cells secrete alkaline phosphatase to cleave the glycan‐bisphosphonate complexes from the implant, which in turn selectively kill the proinflammatory macrophages (“switch‐off”) that have completed their contribution—hence in the manner of “burning bridges”—to promote healing. In vivo examination in an osteoporotic rat model demonstrates that this coating significantly enhances bone‐implant integration (88.4% higher contact ratio) through modulating local inflammatory niches. In summary, a bioresponsive, endogenously triggered, smart coating material is developed to sequentially harness and abolish the power of inflammation to improve osseointegration under osteoporosis, which represents a new strategy for designing immunomodulatory biomaterials for tissue regeneration.