Development of MXene Composite Nanofiber-Based 3D Culture System for the Efficient Generation of MSC-Derived Functional Pancreatic β-Cells

Pancreatic β-cell transplantation is an effective approach for the therapeutic treatment of type I diabetes. However, it has limitations due to the lack of human cadaveric pancreas donors. Stem cells provide an alternative source for the generation of surrogate pancreatic β-cells. Nonetheless, its clinical utility is restricted due to the unavailability of a robust culture system for the generation of large quantities of insulin-responsive pancreatic β-cells. In this study, we fabricated an MXene composite nanofibrous scaffold (PCL 25_Ti₂C 5 nanofiber) for the development of a three-dimensional (3D) culture system that can enhance the proliferation and differentiation of stem cell-derived pancreatic β-cells. The fabricated MXene composite nanofibers exhibited a porous nanostructure and increased hydrophilicity due to a large number of hydrophilic functional groups. We assessed the biocompatibility and differentiation potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) on a fabricated MXene composite nanofibrous scaffold. MXene composite nanofibers significantly upregulated key pancreatic β-cell markers including <i>PDX-1</i>, <i>MAFA</i>, <i>Insulin</i>, <i>Nkx6.1</i>, and <i>Nkx2.2</i> and also showed increased production and secretion of insulin in response to glucose stimulation when compared to control (PCL 25 nanofiber), suggesting enhanced differentiation of hWJ-MSCs into functional pancreatic β-cells. Overall, the results suggest that MXene nanofiber-based cell therapy has therapeutic potential for diabetes treatment.