Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time-and dose-dependent manner
| Autor: | J Nicke, Didem Mumcuoglu, Eric Farrell, Shorouk Fahmy-Garcia, Sebastiaan G. J. M. Kluijtmans, Yanto Ridwan, G.J.V.M. van Osch |
|---|---|
| Přispěvatelé: | Publica, Orthopedics and Sports Medicine, Internal Medicine, Molecular Genetics, Oral and Maxillofacial Surgery, Otorhinolaryngology and Head and Neck Surgery |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male lcsh:Diseases of the musculoskeletal system X-ray microtomography Time Factors Alginates lcsh:Surgery Bone Morphogenetic Protein 2 02 engineering and technology Bone morphogenetic protein 2 Microsphere Injections Rats Sprague-Dawley 03 medical and health sciences In vivo Osteogenesis Transforming Growth Factor beta Injectable delivery system Animals Bone regeneration Calvarial bone defect model Chemistry Slow release Skull Biomaterial Histology lcsh:RD1-811 X-Ray Microtomography Ectopic bone formation model 021001 nanoscience & nanotechnology Microspheres Recombinant Proteins Kinetics 030104 developmental biology Implant Collagen Bone morphogenetic protein-2 lcsh:RC925-935 0210 nano-technology Biomedical engineering |
| Zdroj: | European Cells & Materials, Vol 35, Pp 242-254 (2018) European cells & materials, 35, 242-254. AO Research Institute |
| ISSN: | 1473-2262 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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