Mangiferin- and GNPs/ECPP-loaded platform of UH with dual bi-directional dynamic modulation of stem cells/macrophages and osteoblasts/osteoclasts for the prevention of aseptic loosening

Aseptic inflammation and osteolysis triggered by the phagocytosis of implant wear particles by macrophages are important reasons for aseptic loosening (AL) in total joint replacement, which ultimately leads to implant failure. Therefore, the development of implants with long-term effectiveness in preventing AL is a pressing issue. In contrast to the conventional idea of reducing the occurrence of AL through anti-inflammatory treatment, we prepared implants based on a novel concept: to prevent AL by returning the dynamic balance of osteogenesis/osteolysis through dynamic modulation, which is expected to completely resolve the problem of AL. In this study, a natural polyphenol, mangiferin (MAN), and a composite filler (GNPs/ECPP) were loaded into ultrahigh-molecular-weight polyethylene (UH) to construct a hip implant component with the ability to prevent AL. This modified implant was able to improve the oxidation resistance and wear resistance of implants, which could reduce the production of wear particles, recruit BMSCs as well as promote their proliferation/osteogenic differentiation and inhibit macrophage activity and RANKL-induced macrophage osteoclast differentiation <i>in vitro</i>. These effects suggest that this modified implant has achieved the dual bi-directional dynamic modulation of stem cells/macrophages and osteoblasts/osteoclasts for the prevention of aseptic loosening. Notably, <i>in vivo</i> experiments for implantation of wear-particle-coated titanium rods demonstrated that wear particles from the prepared implant significantly promoted the osseointegration capacity of implanted prosthesis (titanium rod) and effectively inhibited peri-prosthesis osteolysis. This work provides a new concept and presents a promising way for the development of durable implant components with long-term protection against AL.