Controlling the Stem Cell Environment Via Conducting Polymer Hydrogels to Enhance Therapeutic Potential

Stem cells are a promising treatment option for various neurological diseases such as stroke, spinal cord injury, and other neurodegenerative disorders. However, the ideal environment to optimize the therapeutic potential of the cells remains poorly understood. Stem cells in the native environment are influenced by a combination of mechanical, chemical, and electrical cues for proliferation and differentiation. Because of their controllable properties, conductive hydrogels are promising biomaterials to interact with stem cells. Herein, this work develops an interpenetrating conducting polymer hydrogel with tunable mechanical properties. The hydrogel serves as a platform to provide mechanical and electrical cues for interactions with mesenchymal stem cells (MSCs). This work optimizes the formulation of the hydrogel for maximum viability of MSCs and relatively higher cytoskeletal protein expression. The viability of cells is not affected due to electrical stimulation (ES). Further, ES alters the trophic factor secretion of MSCs, with significant increase in VEGF pathway genes—VEGFA and HSPB1. In addition, substrate stiffness of the hydrogel enhances the VEGFB secretion compared to control. Hence, the conducting polymer hydrogel system creates a tunable physical and electrical niche to enhance the therapeutic potential of stem cells for neurological injuries. A conductive interpenetrating network (C‐IPN) hydrogel disc is developed by interpenetrating poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and alginate polymers. The C‐IPN hydrogel maintains a nearly constant impedance independent of changes in frequency and stiffness. As a platform for modulating mechanical and electrical stimulation (ES) of stem cells, the C‐IPN hydrogel endows stem cells with therapeutic potential for neurological injuries.