4.4 Article

High-purity magnesium pin enhances bone consolidation in distraction osteogenesis model through activation of the VHL/HIF-1α/VEGF signaling

Journal

JOURNAL OF BIOMATERIALS APPLICATIONS
Volume 35, Issue 2, Pages 224-236

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/0885328220928550

Keywords

Magnesium; bone defect; distraction osteogenesis; angiogenesis; VHL; HIF-1 alpha; VEGF signaling

Funding

  1. Science and Technology Commission of Shanghai Municipality [18ZR1428700]
  2. Shanghai Sailing Program [17YF1414100]
  3. National Natural Science Foundation of China [81974325, 81702183]

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Distraction osteogenesis has widespread clinical use in the treatment of large bone defects. Nonetheless, the prolonged consolidation period carries the risk of complications. Magnesium-based materials have been shown to promote bone regeneration in fracture healing both in vitro and in vivo. Here, we investigated whether high-purity magnesium could enhance bone formation in distraction osteogenesis. High-purity magnesium pins were placed into the medullary cavity in the rat distraction osteogenesis model. Results showed that the bone volume/total tissue volume, bone mineral density, and mechanical properties of new callus were significantly higher in the high-purity magnesium group compared to stainless steel and control group (p < 0.01). Histological analyses confirmed improved bone consolidation and vascularization in high-purity magnesium group. Further, polymerase chain reaction-array investigation, Western blot, and immunohistochemical results found that vascular endothelial growth factor and hypoxia inducible factor-1 alpha were highly expressed in the high-purity magnesium group, while Von Hippel-Lindau protein was the opposite (p < 0.01). In conclusion, high-purity magnesium implants have the potential to enhance angiogenesis and bone consolidation in the distraction osteogenesis application, and this process might be via the regulation of Von Hippel-Lindau/hypoxia inducible factor-1 alpha/vascular endothelial growth factor signaling.

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