Is human fracture hematoma inherently angiogenic?
This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.
Street
J
J
Department of Academic Surgery, Cork University Hospital, Ireland.
Winter
D
D
Wang
J H
JH
Wakai
A
A
McGuinness
A
A
Redmond
H P
HP
D000328:Adult; D000818:Animals; D002146:Bony Callus / Q000473:pathology*; D002455:Cell Division; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D050723:Fractures, Bone / Q000150:complications; D006406:Hematoma / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008222:Lymphokines / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors