Gelatin Methacrylate as a Mesenchymal Stem Cell Delivery Vehicle: Experimental and Semi-Quantitative Evaluation Under Metabolic Stress.

Abstract

Stem cell-based therapies derived from various sources hold significant potential in regenerative medicine due to their unique properties, particularly their ability to differentiate, self-renew, and modulate the immune system. A polymer-encapsulated Mesenchymal stem cell (MSC) approach can create protective environments for stem cells, enhancing overall therapeutic efficacy. Gelatin Methacrylate (GelMA) is used as a model extracellular matrix to encapsulate MSCs for potential applications in cell-based therapy and bioprinting. This study aims to understand the limitations of GelMA-encapsulation-based cell therapy for an injured tissue. Due to the harsh microenvironment at the implantation site, directly injected stem cells for treatment are affected by factors such as nutrient and oxygen deprivation, immune rejection, reduced cell retention, and inflammatory cytokines. In the current study, we tried to mimic this system. We optimized the GelMA hydrogel cell-encapsulation composition from synthesis through physicochemical characterization, and then tested its cytocompatibility with MSCs. We have further performed numerical modeling to understand and control the behavior of MSCs within the 3D GelMA hydrogel construct under varying metabolic and immunological stress microenvironmental conditions, thereby optimizing the boundary conditions of GelMA-based cell delivery systems.