Collagen microgel-assisted dexamethasone release from PLLA-collagen hybrid scaffolds of controlled pore structure for osteogenic differentiation of mesenchymal stem cells

Abstract

Directed stem cell differentiation over three-dimensional porous scaffolds capable of releasing bioactive instructive cues is an important tool in tissue engineering. In this research, we have prepared dexamethasone (Dex)-releasing collagen microbead-functionalized poly(L-Lactide)-collagen hybrid scaffolds as an osteoinductive platform for human bone marrow-derived mesenchymal stem cells (MSCs). The scaffolds were prepared by a combined method of emulsion freeze-drying and porogen-leaching using pre-prepared ice collagen particulates as a porogen material. Dex release from the hybrid scaffolds was studied at 37 °C under shaking condition and the impact of released Dex towards osteogenic lineage differentiation was investigated by 3 week in vitro culture of MSCs. The results showed that hybrid scaffolds had controlled pore structure and interconnected pores deposited with collagen fibers. The hybrid scaffold facilitated cell seeding and the spatial localization of Dex/collagen microbeads facilitated a microgel-assisted spatio-temporal control of Dex release. The released Dex was useful for osteogenic differentiation of MSCs, which was confirmed from the elevated expression of osteogenic-specific gene-encoded proteins. The hybrid scaffolds should be useful for regeneration of a functional bone tissue.

Keywords:

• porous scaffold
• PLLA-collagen
• microgel
• dexamethasone
• controlled release
• bone regeneration

Acknowledgments

The authors would like to acknowledge the financial support from World Premier International (WPI) Research Centre Initiative, Ministry of Education, Culture, Sports, Science and Technology, Japan.