Bisphosphonate-Functionalized Scaffolds for Enhanced Bone Regeneration

The local sustained release of bioactive substances are attracting increasing attention in bone tissue engineering, which is beneficial to bone tissue formation and helps to improve the bone ingrowth ability of a scaffold. Bisphosphonates (BPs), as a representative kind of osteoclast inhibitors, are proven to possess excellent osteogenic induction capability. Accordingly, various physical and chemical strategies are developed to functionalize bone tissue scaffolds with BPs to achieve controlled release profiles. Compared with traditional treatment modalities, local release of BPs from these composite scaffolds will contribute to continuous bone integration without the risk of many complications. This review explores the molecular mechanisms of BPs on bone metabolism and analyzes the appropriate concentrations of BPs that promote bone regeneration. The advanced BP loading strategies, implant modification technologies, and BP-loaded composite scaffolds based on different matrices are summarized. Finally, the latest advances and the future development of BP-modified scaffolds for enhanced bone regeneration are discussed. This article provides leading-edge design strategies of the BP-functionalized bone engineering scaffolds for improved bone repairability.