Bisphosphonate‐Functionalized Scaffolds for Enhanced Bone Regeneration

Abstract

Bone defect healing is an intricate but methodical process that restores bone integrity and represents an intrinsic capacity of 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.

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

“…It is noteworthy that natural bone is a loose porous multi-ordered structure composed of nano-scale collagen and hydroxyapatite and micro-scale bone plates and pores (Robling et al, 2006;Karsenty et al, 2009;Zhu et al, 2020). To mimic this environment, it is also of great significance to manufacture intraosseous implants with hierarchical micro-nano surface topography (Shah et al, 2018;Cui et al, 2019;Zhang et al, 2019). In our previous work, we fabricated titanium surfaces with hierarchical microprotrusionnanonotch topography using direct metal laser sintering technique together with acid etching treatment, which could promote osteogenic differentiation of stem cells (Zheng et al, 2018).…”

Natural Polymeric Scaffolds in Bone Regeneration

“…Furthermore, the scaffold surface chemistry should allow for functionalization with substances fostering the new osteoid matrix formation: therefore, the specific chemical groups for conjugation with bioactive factors should be numerous and accessible, permitting the application of simple coupling procedures based on either covalent or non-covalent interactions. The material features should also allow to implement strategies for smart, controlled and sustained release of the biomolecules (Liu and Ma, 2004;Wang et al, 2018;Cui et al, 2019). Hence, the selection of the polymer is a critical aspect for scaffold design.…”

Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?

“…[240][241][242] Bisphosphonates have been used for treatment of osteoporosis and hold promise in the regeneration of bone in patients with resorptive bone diseases; they prevent bone resorption by inhibition of osteoclast activity in a concentration-dependent manner. [243,244] Incorporation of ONO-1301, a small molecule synthetic prostacyclin agonist, into a biomimetic nanocomposite scaffold improved MSC proliferation and osteogenic differentiation. [245] Although small molecules have not been used extensively for peripheral nerve regeneration, they have potential to improve neuronal viability, support axonal regeneration over large inter-stump gaps, enhance axonal specificity to end-organ targets, and induce differentiation of various cells into neural lineage cells.…”

“…[ 240–242 ] Bisphosphonates have been used for treatment of osteoporosis and hold promise in the regeneration of bone in patients with resorptive bone diseases; they prevent bone resorption by inhibition of osteoclast activity in a concentration‐dependent manner. [ 243,244 ] Incorporation of ONO‐1301, a small molecule synthetic prostacyclin agonist, into a biomimetic nanocomposite scaffold improved MSC proliferation and osteogenic differentiation. [ 245 ]…”