Abstract
BackgroundFemoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic–osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy.MethodTo improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+.ResultsIn this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone.ConclusionThe therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration.Graphical
Highlights
IntroductionOsteoporotic prosthesis loosening has become a major clinical challenge [1]
With the ageing population, osteoporotic prosthesis loosening has become a major clinical challenge [1]
We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized Porous titanium (PT) can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone
Summary
Osteoporotic prosthesis loosening has become a major clinical challenge [1]. Because osteoclast-mediated bone resorption overwhelms the bone regeneration process induced by osteoblasts, complications such as prosthesis loosening and fracture caused by poor osteointegration are more likely to occur in patients with hip arthroplasty, leading to implant failure [3, 4]. This causes great pain and economic burden to patients and families, so the treatment of osteoporotic integration is a difficult problem in urgent need of a solution. The local drug delivery system can directly influence the microenvironment in the implantation area and effectively regulate bone metabolism The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy
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