Injectable degradable PVA microgels prepared by microfluidic technology for controlled osteogenic differentiation of mesenchymal stem cells

Abstract The direct injection of bone marrow mesenchymal stem cells (hMSCs) is a promising strategy for bone tissue engineering applications. Herein, we have developed injectable degradable poly(vinyl alcohol) (PVA) microgels loaded with hMSCs and growth factors and prepared by a high-throughput microfluidic technology. The PVA-based microgels with tunable mechanical and degradable properties were composed of vinyl ether acrylate-functionalized PVA (PVA-VEA) and thiolated PVA-VEA (PVA-VEA-SH) through a Michael-type crosslinking reaction under mild conditions. The hMSCs sustain high viability in PVA microgels, and cell proliferation and migration behaviors can easily be adjusted by varying crosslinking densities of PVA microgels. Additionally, bone morphogenetic protein-2 (BMP-2) co-encapsulated into the microgel environments enhanced osteogenic differentiation of hMSCs as indicated by a significant increase in alkaline phosphatase activity, calcium content, and Runx2 and OPN gene expression levels. These results demonstrate the degradable PVA microgels with tailored stem cell microenvironments and controlled release profile of the growth factor to promote and direct differentiation. These PVA-based microgels have promising potential as ideal cell vehicles for applications in regenerative medicine. Statement of Significance Stem cell transplantation by an injectable, minimally invasive method has great and promising potential for various injuries, diseases, and tissue regeneration. However, its applications are largely limited owing to the low cell retention and engraftment at the lesion location after administration. We have developed an injectable degradable poly(vinyl alcohol) (PVA) microgel prepared by a high-throughput microfluidic technology and co-loaded with bone marrow mesenchymal stem cells (hMSCs) and growth factor to protect the stem cells from harsh environmental stress and realize controlled cell differentiation in well-defined microenvironments for bone regeneration. We demonstrated that these degradable PVA microgels can be used as stem cell scaffolds with tailored cell microenvironments and controlled release profile of growth factor to promote and direct differentiation. We are convinced that these PVA-based microgels have promising potential in the future as cellular scaffolds for applications in regenerative medicine.