BMP‐2 but not VEGF or PDGF in fibrin matrix supports bone healing in a delayed‐union rat model

Abstract

Treatment of delayed bone healing and non-unions after fractures, osteotomies or arthrodesis still is a relevant clinical challenge. Artificially applied growth factors can increase bone healing and progressively gain importance in clinical routine. The aim of this study was to determine the effects of rhPDGF-BB, rhVEGF-165, and rhBMP-2 in fibrin matrix on bone healing in a delayed-union rat model. Thirty-seven rats underwent a first operation where a standardized femoral critical size defect was created. A silicone spacer was implanted to impair vascularization within the defect. At 4 weeks the spacer was removed in a second operation and rhPDGF-BB, rhVEGF-165, or rhBMP-2 were applied in a fibrin clot. Animals in a fourth group received a fibrin clot without growth factors. At 8 weeks fibrin bound rhBMP-2 treated animals showed a significantly increased union rate and bone volume within the defect compared to the other groups. Single application of fibrin bound rhPDGF-BB and rhVEGF-165 failed to increase bone healing in our atrophic non-union model. ß

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

“…As a consequence osseous unions as well as narrow unions occurred in 2 out of 6 animals respectively. The results are supported by a previous study [32].…”

Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair

“…These effects may explain why VEGF has been found to enhance bone healing and regeneration in many studies but has failed to have positive effects in others using ex vivo VEGF gene therapy or recombinant VEGF (13,(46)(47)(48). An important conclusion from the present study is that optimal amounts of VEGF are critical for the therapeutic outcome.…”

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

“…Although many studies have reported a positive correlation between PDGF administration and enhanced bone healing, these observations were not shared by all. Kaipel et al (2012) demonstrated the failure of PDGF treatment to increase bone healing within a femoral segmental defect in rat. The same study also demonstrated failed healing following administration of another angiogenic factor VEGF.…”

“…However, selection according to the task at hand, whereby combination treatment with FGF-2 may be required to induce void filling callus formation and osteoid production prior to combination treatment with BMP-2 for mineralisation. A staged approach may be necessary for efficient and effective bone healing requiring multiple growth factors delivered spatiotemporally in (Lee et al, 2001b) and rat (Kaipel et al, 2012) for bone tissue engineering strategies (Supplementary Table 4). …”