Mechanical stability affects angiogenesis during early fracture healing

Objectives: The goal of this study was to determine to what extent mechanical stability affects vascular repair during fracture healing. Methods: Stabilized and nonstabilized tibia fractures were created in adult mice. Fracture tissues were collected at multiple time points during early fracture healing. Vasculature in fractured limbs was visualized by immunohistochemistry with an anti-PECAM-1 antibody on tissue sections and then quantified with stereology. Oxygen tension, vascular endothelial growth factor expression, and lactate accumulation at the fracture site were measured. Gene expression was compared between stabilized and nonstabilized fractures by microarray analysis. Results: We found that new blood vessel formation was robust by 3 days after fracture. Quantitative analysis showed that nonstabilized fractures had higher length density and surface density than stabilized fractures at 3 days after injury, suggesting that nonstabilized fractures were more vascularized. Oximetry analysis did not detect a significant difference in oxygen tension at the fracture site between stabilized and nonstabilized fractures during the first 3 days after injury. Further microarray analysis was performed to determine the effects of mechanical stability on the expression of angiogenic factors. No significant difference in the expression of vascular endothelial growth factors and other angiogenic factors was detected between stabilized and nonstabilized fractures. Conclusions: Mechanical instability promotes angiogenesis during early fracture healing and further research is required to determine the underlying mechanisms.