Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 107, Issue 10, Pages 2282-2295Publisher
WILEY
DOI: 10.1002/jbm.a.36737
Keywords
BM-MSCs; BMP-2; bone regeneration; dural delivery; multicore PLA microspheres
Funding
- Nature Science Foundation of Hunan Province, China [2018JJ3766]
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Stem cell-based therapies provide a promising approach for bone repair. In the present work, we developed a novel 3D vehicle system for dual-delivery of encapsulated bone marrow mesenchymal stem cells (BM-MSCs) and bone morphogenetic protein-2 (BMP-2) for treatment of large bone defects. The vehicle system consists of sodium alginate microcapsules and polylactic acid (PLLA) microspheres. BM-MSCs are encapsulated in the microcapsules, and BMP-2 proteins are encapsulated in the PLLA microspheres. This vehicle system acted as a multicore structure for sustained release of BMP-2, which enabled pulsed dosing induction of osteogenic differentiation of the co-embedded BM-MSCs. in vitro experiments showed that the loaded BMP-2 was constitutively released up to 30 days. Bioactivity of the incorporated BMP-2 in the microspheres was preserved and osteogenic differentiation of the BM-MSCs in the microcapsules was improved. In vivo, osteogenesis studies demonstrated that satisfactory degree of repair of a rat calvarial defect was achieved with the delivery of either encapsulated BM-MSCs alone or encapsulated BMP-2 alone. Transplantation of encapsulated both BM-MSCs and BMP-2 exhibited the greatest repair potential following 4- or 8-weeks treatment. In conclusion, microencapsulation of BM-MSCs and BMP-2 promoted the maturity of newly generated bone and improved new bone formation. Transplantation of BM-MSCs and BMP-2 in our novel 3-D vehicle system is a promising strategy for regenerative therapies of large bone defects.
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