The aim of the current study was to reduce the clinically used supra-physiological dose of bone morphogenetic protein-2 (BMP-2) (usually 1.5 mg/mL), which carries the risk of adverse events, by using a more effective release system. A slow release system, based on an injectable hydrogel composed of BMP-2-loaded recombinant collagen-based microspheres and alginate, was previously developed. Time-and dose-dependent subcutaneous ectopic bone formation within this system and bone regeneration capacity in a calvarial defect model were investigated. BMP-2 doses of 10 µg, 3 µg and 1 µg per implant (50 µg/mL, 15 µg/mL and 5 µg/mL, respectively) successfully induced ectopic bone formation subcutaneously in rats in a time-and dose-dependent manner, as shown by micro-computed tomography (µCT) and histology. In addition, the spatio-temporal control of BMP-2 retention was shown for 4 weeks in vivo by imaging of fluorescently-labelled BMP-2. In the subcritical calvarial defect model, µCT revealed a higher bone volume for the 2 µg of BMP-2 per implant condition (50 µg/mL) as compared to the lower dose used (0.2 µg per implant, 5 µg/ mL). Complete defect bridging was obtained with 50 µg/mL BMP-2 after 8 weeks. The BMP-2 concentration of 5 µg/mL was not sufficient to heal a calvarial defect faster than the empty defect or biomaterial control without BMP-2. Overall, this injectable BMP-2 delivery system showed promising results with 50 µg/mL BMP-2 in both the ectopic and calvarial rat defect models, underling the potential of this composite hydrogel for bone regeneration therapies.

Additional Metadata
Keywords Bone morphogenetic protein-2, Calvarial bone defect model, Ectopic bone formation model, Injectable delivery system, Slow release
Persistent URL dx.doi.org/10.22203/eCM.v035a17, hdl.handle.net/1765/114824
Journal European Cells & Materials
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/607051 - BIO INSPIRED BONE REGENERATION (BIO-INSPIRE)
Citation
Mumcuoglu Guvenc, Z.D, Fahmy-Garcia, S. (S.), Ridwan, Y, Nickel, J. (J.), Farrell, E, Kluijtmans, S.G.J.M, & van Osch, G.J.V.M. (2018). Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time-and dose-dependent manner. European Cells & Materials, 35, 242–254. doi:10.22203/eCM.v035a17