Functionalized anti-osteoporosis drug delivery system enhances osseointegration of an inorganic–organic bioactive interface in osteoporotic microenvironment

Abstract

Osteoporosis leads to various complications, such as prosthesis loosening and periprosthetic fracture, after joint replacement. This is mainly due to the impaired osteogenesis and excessive osteoclastic activity in osteoporotic microenvironment, which leads to insufficient osseointegration between prostheses and host bone. In this study, a functional drug-releasing inorganic–organic bioactive interface was constructed, comprising inorganic three-dimensional (3D) printed porous titanium alloy interface and organic poloxamer 407 temperature-sensitive hydrogel loaded with a novel anti-osteoporosis drug (technetium methylenediphosphonate, 99Tc-MDP). The inorganic–organic bioactive interface showed good biocompatibility and exhibited a sustained release profile. This performance enhanced osteogenic differentiation, inhibited the expression of osteoclast-related genes and inhibited the osteoclastogenesis, as compared with traditional bisphosphonates (alendronate) in vitro. When implanted into the distal femoral defect using an osteoporotic rabbit model, the 99Tc-MDP-loaded bioactive interface exhibited the most stable osseointegration with native bone. Furthermore, the drug delivery system inhibited osteoclastic activity via regulation of the osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) signaling pathway, which significantly ameliorated the osteoporosis status to effectively prevent continuous bone destruction around the interface. This study has clinical significance, as it demonstrates that the 99Tc-MDP modified inorganic–organic interface serve as a novel artificial prosthetic interface for patients with poor osteogenesis.

Keywords

• Drug delivery system
• Inorganic-organic bioactive interface
• Interface osseointegration
• OPG/RANKL signaling pathway
• Osteoporotic microenvironment