Spatially controlled rhBMP-2 mediated calvarial bone formation in a transgenic mouse model
Shalini V Gohil1, Liping Wang2, David W Rowe2
1Department of Orthopedic Surgery, UConn Health, Farmington, CT, 06030, United States; Institute for Regenerative Engineering, The Raymond Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT, 06030, United States.
International Journal of Biological Macromolecules
|August 30, 2017
Summary
Injectable glycol chitosan hydrogel effectively delivered recombinant human bone morphogenetic protein-2 (rhBMP-2), promoting complete bone defect healing. This localized delivery enhanced osteogenic activity compared to traditional collagen hydroxyapatite scaffolds.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Skeletal Biology
Background:
- Bone morphogenetic proteins are crucial for osteogenesis.
- Effective delivery systems are needed to localize BMPs and enhance bone regeneration.
- Current scaffolds may suffer from rapid diffusion of growth factors.
Purpose of the Study:
- To evaluate the localized osteogenic activity of rhBMP-2 delivered via injectable glycol chitosan hydrogel.
- To compare the efficacy of this hydrogel system against a collagen hydroxyapatite scaffold (Healos®).
- To assess the spatial control and bioactivity of rhBMP-2 at the cellular level.
Main Methods:
- Utilized a critical-sized bilateral calvarial defect model in rodents.
- Implanted rhBMP-2 loaded hydrogel (HPP-GC+BMP) in one defect and Healos® in the contralateral defect.
- Employed histological, histomorphometric, and fluorescence analysis using Col3.6 transgenic animals.
Main Results:
- HPP-GC+BMP implantation resulted in complete calvarial defect closure within 4 weeks.
- No significant bone formation was observed at the Healos® implanted site.
- Histological analysis confirmed localized osteoprogenitor recruitment and osteogenesis at the HPP-GC+BMP site.
- The hydrogel minimized diffusive loss of rhBMP-2.
Conclusions:
- Enzymatically crosslinkable glycol chitosan hydrogel is an effective delivery vehicle for rhBMP-2.
- This system demonstrates superior localized osteogenic activity and bone regeneration compared to Healos®.
- The HPP-GC hydrogel provides spatial control over rhBMP-2 bioactivity, enhancing bone healing efficacy.
