Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model

Abstract

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model. Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 microg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Osteogenic factors primarily belong to the TGF-β superfamily, and the most studied factors are bone morphogenetic protein BMP2, BMP4, BMP6 and BMP7 [16,17]. Because vascularization is essential for bone regeneration, angiogenic factors VEGF, PDGF, FGF and IGF are also being extensively tested for their usefulness in bone repair [18][19][20][21][22][23][24]. Immunomodulatory and anti-inflammatory agents, such as selective anti-cytokine therapies, corticosteroids and non-steroidal anti-inflammatory drugs, are used to direct specific effects on the regeneration and resorption pathways during bone healing [25,26].…”

Mobilization of endothelial precursor cells: Systemic vascular response to musculoskeletal trauma

“…1,2 Efforts to enhance fracture neovascularization by supplementing with recognized proangiogenic cytokines have yielded promising results. [3][4][5][6]39 However, the resident population of endothelial cells that is responsive to available levels of angiogenic growth factors may potentially limit the extent to which supplementation enhances tissue neovascularization. Situations which classically exhibit compromised endothelial function and angiogenesis are well recognized in contributing to the significant complications of delayed fracture healing and atrophic non-union.…”

Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury

“…Neurohormonal or neurohumoral mechanisms were also suggested. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Growth factors and cytokines are proteins that serve as signaling molecules for cells. They influence critical functions as cell division, matrix synthesis, and tissue differentiation.…”

“…The results of experimental studies have established that growth factors and cytokines play an important role in fracture healing and repair of musculoskeletal tissue. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The objective of this prospective controlled study was to investigate the effect of spinal cord injury and concomitant long bone fractures on the serum level of growth factors and cytokines, rather than bone morphogenetic protein (BMP) growth factor.…”