VEGF-activated angiogenesis during bone regeneration.
OBJECTIVE
The aim of this study was to investigate the influence of controlled release of recombinant human vascular endothelial growth factor (rhVEGF(165)) on angiogenesis and osteogenesis in a mandibular defect model.


METHODS
A total of 56 rabbits were operated and bicortical holes were placed at the lower border of the mandible. The defects were filled with type-I collagen, with collagen complexed with 0.8 mug rhVEGF(165), or left without any filling. After 3, 7, 14, and 28 days, specimens were taken and histologic, histomorphometric, and immunohistologic analyses were carried out concerning number of vessels, cross-sectional area of vessels, and area and density of regenerated bone.


RESULTS
Bone formation occurred in a typical centripetal direction and showed all stages of bone regeneration and maturation. New vessel formation took place in front of the osteogenic regeneration front. The number of vessels increased in all groups until day 14, followed by physiologic regression in the control groups as opposed to persisting high numbers in the study group. The area of newly formed bone showed no difference to the control group but the density of regenerated bone was significantly higher in the study group.


CONCLUSIONS
Blood vessels are an important component of bone formation and maintenance and the bone tissue differentiation is related to the local presence of blood vessels. The activation of angiogenesis using rhVEGF(165) leads to more intensive angiogenesis and bone regeneration.
Kleinheinz
Johannes
J
Department of Cranio-Maxillofacial Surgery, University Hospital Muenster, Germany. joklein@uni-muenster.de
Stratmann
Udo
U
Joos
Ulrich
U
Wiesmann
Hans-Peter
HP
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D024042:Collagen Type I / Q000494:pharmacology; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D006097:Granulation Tissue / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008334:Mandible / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D024042:Collagen Type I; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A