3D printed porous biomimetic composition sustained release zoledronate to promote osteointegration of osteoporotic defects

Abstract

Patients with osteoporosis are more likely to suffer prosthesis displacement, subsidence or periprosthesis fracture after prosthesis replacement. This is due to excessive osteoclast activity and a lack of bone marrow mesenchymal stem cell (BMSC) integration at the implant-bone interface locally in the setting of osteoporosis. In order to inhibit local excessive bone resorption and promote bone integration, we have constructed a porous titanium/poloxamer 407 hydrogel system loaded with zoledronate (ZOL), a bisphosphonate, to promote osteointegration in a rabbit model of osteoporosis. This composite scaffold (ZOL/gTi) showed good biocompatibility and sustained ZOL release along with the degradation of hydrogel. Not only does this system provide a three-dimensional structural network for BMSC proliferation but also locally released ZOL promotes proliferation and osteogenic differentiation while inhibiting osteoclast differentiation of BMSCs in vitro. After implantation of ZOL/gTi into a distal femoral defect in the rabbits, micro-CT, histological, push-out, as well as genetic and protein analyses revealed significant promotion of osteointegration with the aid of this composite scaffold. Here, we provide an important theoretical basis for the research and development of bioactive implant interfaces for patients with osteogenic defects, such as osteoporosis.