Endogenous repair theory enriches construction strategies for orthopaedic biomaterials: a narrative review

Yizhong Peng, Jinye Li, Hui Lin, Shuo Tian, Sheng Liu, Feifei Pu, Lei Zhao, Kaige Ma, Xiangcheng Qing, Zengwu Shao

Figure 3. Endogenous cellular changes after bone fracture. When a bone is fractured, the MSCs migrate to the bone defect area and differentiate into osteoblasts to form and remodel the bone matrix. In the end, approximately 15% of the osteoblasts become embedded in the bone matrix as osteocytes, 30% of the osteoblasts become quiescent bone lining cells, and the remaining 40–70% of the osteoblasts are likely to undergo death by apoptosis. The apoptotic osteoblasts expressing certain signals are efficiently cleared by macrophages in a process called efferocytosis. This process is initiated by the expression of the apoptotic signals on osteoblasts and is activated by the binding of linking proteins, including MFG-E8 or Gas6, and macrophage proteins, such as αvβ3 or Mer. The efferocytosis-induced production of specific proteins, such as TGF-β, may promote continuous bone modelling by recruiting osteoblasts from progenitor cells.29 Gas6: growth arrest-specific 6; M-CSF: macrophage colony-stimulating factor; MER (tk): receptor tyrosine kinase MerTK; MFG-8: milk fat globule-epidermal growth factor 8; MSCs: mesenchymal stromal cells; OB: osteoblasts; OC: osteoclasts; RANK: receptor activator of nuclear factor-κB; RANKL: receptor activator of nuclear factor-κB ligand; TGF-β: transforming growth factor β; αvβ3: alpha-V beta-3 integrin.