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

Abstract

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.

Conductive gradient hydrogels allow spatial control of adult stem cell fate

“…4,22 A frequency of 20 Hz was chosen as it ensures stable conductivity through the hydrogel but not PBS (ionic conductivity). 19…”

“…Electrical stimulation has shown to induce several transcription factors that are involved in cell self-renewal and survival, cell differentiation, synaptic remodeling, neural regeneration. [4][5][6][7]19,[21][22][23][24][25] We hypothesized that the electrical stimulation and electrical gradient would influence differentiation changes and properties of the hMSCs. The unstimulated condition (CGG + Basal) showed fewer stained cells on the surface due to the lack of cellular attachment as described above (Fig.…”

“…4,22 A frequency of 20 Hz was chosen as it ensures stable conductivity through the hydrogel but not PBS (ionic conductivity). 19 Cellular response on electrically-stimulated CGGs Cells were maintained in the basal medium condition (Basal) to exclude any potential chemical effects on proliferation and induction (see Section 2. Materials and Methods).…”

“…In addition, conductive hydrogels can be electrically stimulated which can be highly relevant and desirable in mimicking electrical activities for neural engineering applications. 19,20 Developing new interactive conductive hydrogels that display gradual changes in electrical field strength is highly desirable to study the cellular response in a more physiological relevant manner.…”

Importance of Molecular and Bulk Dynamics in Supramolecular Hydrogels in Dictating Cellular Spreading

“…Nature uses a variety of supramolecular interactions to create functional materials with different mechanical, dynamic, and bio­(chemical) properties, i.e., soft tissues, such as those in the brain, and stiff tissue, such as those in bone . Inspired by biology, synthetic mimics of the environment around cells, better known as the extracellular matrix (ECM), hold great promise in many fields including regenerative medicine and wearable electronics. – Using the chemistry of materials, flexible electronic materials are being developed that can interact with living tissue, with pioneering contributions by the Reichmanis lab and Bao laboratories. ,,– Moving toward the field of regenerative medicine, chemistry of materials is also being employed here to accurately mimic the native ECM to grow cells into more complex living tissues, of which hydrogels are an important and emerging class. ,– As accurate ECM mimics, such hydrogels must possess similar and preferably independently controllable mechanical, dynamic, and bioactive properties as those of the native ECM. – …”