The treatment of segmental bone defects in rabbit tibiae with vascular endothelial growth factor (VEGF)-loaded gelatin/hydroxyapatite “cryogel” scaffold

Abstract

The aim of this study was to investigate the effectiveness of a novel hydroxyapatite containing gelatin scaffold--with and without local vascular endothelial growth factor (VEGF) administration--as the synthetic graft material in treatment of critical-sized bone defects. An experimental nonunion model was established by creating critical-sized (10 mm. in length) bone defects in the proximal tibiae of 30 skeletally mature New Zealand white rabbits. Following tibial intramedullary fixation, the rabbits were grouped into three: The defects were left empty in the first (control) group, the defects were grafted with synthetic scaffolds in the second group, and synthetic scaffolds loaded with VEGF were administered at bone defects in the third group. Five rabbits in each group were killed on 6th and 12th weeks, and new bone growth was assessed radiologically, histologically and with dual-energy X-ray absorptiometry (DEXA). At 6 weeks, VEGF-administered group had significantly better scores than the other two groups. The second group also had significantly better scores than the control group. At 12 weeks, while no significant difference was noted between the second and third groups, these two groups both had significantly better scores in all criteria compared with the control group. There were no signs of complete fracture healing in the control group. The administration of hydroxyapatite containing gelatin scaffold yielded favorable results in grafting the critical-sized bone defects in this experimental model. The local administration of VEGF on the graft had a positive effect in the early phase of fracture healing.

Bone regenerative medicine: classic options, novel strategies, and future directions

“…More immunopositive osteoclast and mesenchymal cells were found in the bone tissue from animals treated with TGF-β1 compared with the control group. Ozturk et al [130] investigated the role of a novel hydroxyapatite containing gelatin scaffold with and without local vascular endothelial growth factor as the synthetic graft material in the treatment of critical-sized tibial bone defects in rabbits. After 6 weeks, the administration of VEGF on the graft exerted a positive effect in the early phases of fracture healing but had no effect after 12 weeks.…”

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].…”

Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks coated with rhVEGF165 in critical-size alveolar bone defects in vivo

“…Additionally, scaffolds can also act as carriers for growth factors with biological properties, such as bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF). 12,13 Coralline hydroxyapatite (CHA) is one of the synthetic porous biomaterials among numerous xenogenous grafting materials and is made by partially converting calcium carbonate from coral to a hydroxyapatite (HA) layer on the surface via a hydrothermal exchange. CHA is a composite scaffold with an outer HA layer and an inner coralline core.…”