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Vascular Endothelial Growth Factor Gene‐Activated Matrix (VEGF 165 ‐GAM) Enhances Osteogenesis and Angiogenesis in Large Segmental Bone Defects
Author(s) -
Geiger Florian,
Bertram Helge,
Berger Irina,
Lorenz Helga,
Wall Olga,
Eckhardt Christina,
Simank HansGeorg,
Richter Wiltrud
Publication year - 2005
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.050701
Subject(s) - angiogenesis , vascular endothelial growth factor , cd31 , bone healing , vascularity , wound healing , vascular endothelial growth factor a , pathology , medicine , biology , anatomy , immunology , vegf receptors
Healing of fractures is dependent on vascularization of bone, which is in turn promoted by VEGF. It was shown that 0.1 and 1 mg of pVEGF 165 ‐GAM led to a significant increase in vascularization and bone regeneration in defects that would otherwise have led to atrophic nonunions. Introduction : One reason for lack of bone healing in nonunions is the absence of vascularization. In skeletogenesis, which is tightly linked to angiogenesis, vascular endothelial growth factor (VEGF) promotes the vascularization of the growth plate and transformation of cartilage to bone. We postulate that a gene‐activated matrix (GAM), created with a plasmid coding for human VEGF 165 , coated on a collagen sponge could efficiently accelerate bone healing in large segmental defects. Materials and Methods : Sixty New Zealand white rabbits received a 15‐mm critical size defect on one radius, which was filled with either 0.1 or 1 mg plasmid‐DNA as GAM. Radiographs were obtained every 3 weeks. After 6 or 12 weeks, animals were killed. New bone was measured by μCT scans. Vascularity was measured using anti‐CD31 staining of endothelial cells in 18 regions of interest per implant. Results : Scaffold and control plasmid showed no defect healing, whereas most of the animals in the VEGF groups showed partial or total bone regeneration. Significantly more bone was found in the VEGF groups, with no significant differences between the 0.1‐ and 1‐mg groups. Immunohistochemical staining of endothelial cells revealed that the VEGF groups showed two to three times the number of vessels and a significantly larger endothelial area after 6 weeks. Twelve weeks after surgery, the amount of vascularization decreased, whereas more new bone was detectable. Conclusions : The rabbit critical size defect was appropriate in size to produce atrophic nonunions. We showed that angiogenesis and osteogenesis can be promoted by a VEGF 165 ‐GAM that is an appropriate tool to induce bone healing in atrophic nonunions.