2022, Vol. 26 ›› Issue (36): 5881-5888

Mechanism of bone healing and angiogenesis during distraction osteogenesis

Lyu Zichen, Tu Zhenxing, Xu Ao, Cheng Kang, Wang Hongtao, Wang Bin   

Abstract: BACKGROUND: Ilizarov technology has become one of the indispensable technological tools for orthopedic, maxillofacial surgery and prosthetic and reconstructive surgeons worldwide, but the mechanism of bone healing and angiogenesis in the process of distraction osteogenesis is not very clear.  
OBJECTIVE: To review the microstructure and molecular mechanisms of bone healing and angiogenesis during distraction osteogenesis.
METHODS: The articles on the mechanisms of bone healing and angiogenesis in the distraction osteogenesis process in recent years were reviewed on PubMed and CNKI. Duplicate articles and duplicate studies were excluded, while the included articles were reviewed and analyzed.  
RESULTS AND CONCLUSION: (1) There is a 3rd ossification mechanism in distraction osteogenesis distinct from simple fracture healing, “transchondral osteogenesis”. (2) During the healing process of distraction osteogenesis, bone stumps form microcolumn forming zones on both sides and eventually lead to interfibrillar zones, and complete mineralization and remodeling of the newly formed bone during the consolidation phase. (3) Factors such as interleukins, bone morphogenetic proteins and the RANKL/OPG system have different spatiotemporal distributions during distraction osteogenesis, but all play a role in promoting bone formation or remodeling. (4) The process of distraction osteogenesis is accompanied by substantial neoangiogenesis and is highly consistent with the osteogenic cycle, whereas neovascularization and mineralization are the beginnings of bone regeneration. (5) Endothelial progenitor cells and cytokines such as vascular endothelial growth factor play a role in neoangiogenesis by promoting revascularization and mineralization in the distraction area, and their expression is regulated by the inflammatory response and stretch after osteotomy, whereas the induced homing of endothelial progenitor cells to the site of bone regeneration is an important factor in the angiogenesis of distraction osteogenesis. (6) Bone healing is mutually promoted and coupled with angiogenesis. The two ends of the osteotomy form a collagen fiber bundle under traction force, which eventually advances to the interfibrillar zone, where osteoblasts line up, gradually ossify, and undergo consolidation and remodeling to form mature, lamellar bone with bone marrow. Angiogenesis precedes the healing of bone and can occur after osteotomy, with blood vessels on the periosteal and endosteal surfaces at both ends of the osteotomy gradually proliferating and leading to interfibrillar zones, followed by complete communication of periosteal and medullary vascular networks at the distraction site. (7) The current study cannot fully explain the macro - and micro processes of distraction osteogenesis and the roles of various influencing factors and cytokines in distraction osteogenesis, and the healing mechanism of distraction osteogenesis needs further study.
Key words: distraction osteogenesis, fracture healing, angiogenesis, interfibrillar zone, endothelial progenitor cells, cytokines, bone morphogenetic protein, vascular endothelial growth factor