A Comparative Analysis of the Osteogenic Effects of BMP-2, FGF-2, and VEGFA in a Calvarial Defect Model

Abstract

The utilization of growth factors for bone regeneration is a widely studied field. Since the approval of bone morphogenetic protein-2 (BMP-2) for therapeutic use in humans, the concept of utilizing growth factors for bone regeneration in translational medicine has become even more attractive. Despite many studies published on individual growth factors in various bone models, comparative analysis is largely lacking. The aim of our study was to compare three different proosteogenic factors under identical in vivo conditions. Thus, we tested the bone regeneration capacity of the three different growth factors BMP-2, fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor A (VEGFA) in a calvarial defect model. We demonstrated that BMP-2 and VEGFA had similar bone healing capacities, resulting in complete calvarial healing as early as week 3. FGF-2 also showed a significantly higher bone regeneration capacity; however, the healing rate was lower than with BMP-2 and VEGFA. Interestingly, these findings were paralleled by an increased angiogenic response upon healing in BMP-2-and VEGFA-treated calvarial defects as compared with FGF-2. Immunohistochemistry for proliferating and osteoprogenitor cells revealed activity at different points after surgery among the groups. In conclusion, we demonstrated an efficient bone regeneration capacity of both BMP-2 and VEGFA, which was superior to FGF-2. Moreover, this study highlights the efficient bone regeneration of VEGFA, which was comparable with BMP-2. These data provide a valuable comparative analysis, which can be used to further optimize growth factor-based strategies in skeletal tissue engineering.

Fibroblast growth factor signaling in skeletal development and disease

“…In addition to promoting angiogenesis, VEGF controls bone formation by stimulating the differentiation of mesenchymal stem cells to osteoblasts (Liu and Olsen 2014). Accordingly, VEGF alone has a potent bone repair potential by promoting angiogenesis and osteogenesis in vivo (Behr et al 2012). Since FGF2 promotes Vegf expression in osteoblasts (Takai et al 2007), these two factors may promote bone repair through activation of both angiogenesis and osteogenesis.…”

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

“…Additionally, the use of parathyroidal hormone (PTH), growth hormone, steroids, calcitonin and vitamin D in systemic applications has also been shown to advance bone healing through stimulating osteogenesis, angiogenesis and osteoblast differentiation [27][28][29][30]. Various combinations of biomolecules have also been extensively evaluated in pre-clinical models with mostly positive results [27,[31][32][33][34][35][36][37].…”

Small Molecule Inhibition of Transforming Growth Factor Beta Signaling Enables the Endogenous Regenerative Potential of the Mammalian Calvarium

“…For this aim, 2-mm calvarial defects were created in the parietal bone of pN10 mice as previously described. 49 A collagen sponge was then placed into the defect with either 200 mL of 26 mM SB431542 or 200 mL of vehicle DMSO, which served as a control. After surgery, mCT analysis was performed at different time points (Fig.…”