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. 2011 Aug;25(8):494-9.
doi: 10.1097/BOT.0b013e31822511e0.

Mechanical stability affects angiogenesis during early fracture healing

Chuanyong Lu  1 , Neema Saless, Diane Hu, Xiaodong Wang, Zhiqing Xing, Huagang Hou, Benjamin Williams, Harold M Swartz, Celine Colnot, Theodore Miclau, Ralph S Marcucio
Affiliations

Mechanical stability affects angiogenesis during early fracture healing

Chuanyong Lu et al. J Orthop Trauma. 2011 Aug.

Abstract

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.

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Conflict of interest statement

Conflicts of Interest For the remaining authors none were declared.

Figures

Fig. 1
Fig. 1
Non-stabilized tibia fractures were more vascularized at 3 days after injury. (A) PECAM immunohistochemistry showed blood vessels (black color) in the fracture site of non-stabilized fractures. (B) Less blood vessels were detected at the fracture site of stabilized fractures. (C) Length density and (D) surface density of blood vessels in the fractured tibiae. Scale bars in A and B = 500um. In C and D, * p<0.05, ** p<0.01.
Fig. 2
Fig. 2
Tissue levels of VEGF and lactate in stabilized and non-stabilized fractures. * p<0.05. # p<0.05 compared to unfractured controls.
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