Date of Award

Summer 8-24-2017

Degree Type

Thesis

Degree Name

MSOB (Master of Science in Oral Biology)

Primary Advisor

Dr. Hyun Duck Nah

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a clinically available osteogenic growth factor. In its current form, approved for clinical use, however, the growth factor is delivered in excessively high doses, resulting in unpredictable bone growth and unwanted clinical side effects. In this study, we evaluated a novel system, slow-release hybrid delivery system for PLGA- rhBMP-2 microcapusles in combination with BM MSC spheroids, and assess if it can lead to improved BMP-derived bone formation. The first aim of this study is to evaluate the osteogenicity of 3D cell spheroids as compared to 2D cultured cells, as we used primary cells that harvested from transgenic GFP mice. Second, we evaluated the effect of rhBMP2/PLGA microcapsules embedded within 3D cell spheroid constructs. Lastly, we combined the delivery of rhBMP2/PLGA microcapsule-containing spheroids and Matrigel to assess the bone formation in an in vivo model, as the combined effect of BMP microcapsules and spheroids has not been studied before. We found that by culturing BM MSCs in the spheroid form increases the osteogenic potential versus culturing the cells in a 2D monolayer both in vitro and in vivo. Further we concluded that incorporating BMP microcapsules in our BM MSC spheroid construct further increases the osteogenic potential compared to spheroid constructs which did not contain rhBMP-2 microcapsules. Our results suggest that the BM MSC spheroid constructs containing microfluidic BMP2-PLGA microcapsules were effective in bone regeneration even when rhBMP-2 was used at a low dosage in the construct and therefore this model could be a viable model for bone tissue engineering.

Comments

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