Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time-and dose-dependent manner

D. Mumcuoglu, S. Fahmy-Garcia, Y. Ridwan, J. Nickel, E. Farrell, Sebastiaan G.J.M. Kluijtmans, G.J.V.M. van Osch

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

29 Citaten (Scopus)
227 Downloads (Pure)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)242-254
Aantal pagina's13
TijdschriftEuropean Cells and Materials
Volume35
DOI's
StatusGepubliceerd - 26 apr 2018
Extern gepubliceerdJa

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