Hydrogel-Encapsulated Primed Mesenchymal Stem Cells Enhance Regeneration and Immune Modulation in Full-Thickness Burn Wounds

Mesenchymal stem cells (MSCs) have shown regenerative and antimicrobial potential; however, their therapeutic efficacy is constrained by poor survival and engraftment. Here, we demonstrate that priming MSCs with insulin-secreting cells (ISCs) and encapsulating them in hydrogels (HEMI) enhances their regenerative function, leading to accelerated healing of full-thickness burns in a porcine model.

Wounds treated with HEMIs achieved 80% closure within five weeks, compared to 50% in MSC-only and 0% in standard-of-care controls. Histological analysis revealed complete epidermal and dermal regeneration with minimal fibrosis in HEMI-treated wounds. Single-cell RNA sequencing (scRNA-seq) and differentially abundant sequencing (DA-seq) analysis identified distinct MSC subpopulations transitioning from a proliferative to a tissue-remodeling phenotype, with insulin priming promoting pathways involved in extracellular matrix (ECM) stabilization, immune modulation, and oxidative stress resistance.