Microfluidic-based fabrication of alginate microparticles for protein delivery and its application in the in vitro chondrogenesis of mesenchymal stem cells

Hydrogel microparticles have been exploited extensively as protein carriers for drug delivery and tissue regeneration. Thus, a high-throughput and controllable fabrication method is required. This study introduces a droplet-based microfluidic approach to synthesize alginate microparticles using a double flow-focusing polydimethylsiloxane (PDMS) microdevice for protein encapsulation purposes. Alginate droplets were formed by the shear stress of the mineral oil flow on the alginate flow and were instantaneously gelated into alginate microparticles with the co-flow of CaCl2. With this microdevice, the size of alginate microparticles could be controlled freely via the flow rates of the input fluids. The synthesized alginate microparticles encapsulated with bovine serum albumin exhibited a fast release pattern in phosphate-buffered saline. Furthermore, an injectable collagen scaffold embedded with transforming growth factor beta 3 (TGF- beta 3) encapsulated alginate microparticles was synthesized and demonstrated high viability of human mesenchymal stem cells (MSCs), with over 90% in living cells after five days of culturing. Moreover, the results related to the sulfated glycosaminoglycan content and cartilage staining of the composite scaffold proved that the TGF- beta 3 released from the alginate microparticles could induce the chondrogenesis of MSCs. Therefore, the proposed microdevice has good potential for use in fabricating alginate microparticles for biomedical applications.

Automated summary

This study introduces a droplet-based microfluidic approach to synthesize alginate microparticles for protein encapsulation, demonstrating precise control over particle size, good drug release patterns, and high viability of cells. The release of TGF-beta 3 from the alginate microparticles induced chondrogenesis of MSCs, showing great potential for biomedical applications.