Probing the effects of polysaccharide hydrogel composition on the viability and pro-angiogenic function of human adipose-derived stromal cells

This study investigates how polysaccharide hydrogel composition modulates the viability and pro-angiogenic function of encapsulated human adipose-derived stromal cells (hASCs) for cell therapy in critical limb ischemia. Methacrylated glycol chitosan (MGC), methacrylated hyaluronic acid (MHA), and composite MGC + PEG(PTMC-A)₂ hydrogels were synthesized with matched stiffness (~4 kPa) to decouple compositional effects from mechanical cues. Encapsulation studies revealed >85% hASC viability in single-phase hydrogels over 14 days, while MGC-based systems promoted higher secretion of pro-angiogenic cytokines (VEGF, HGF, IL-6, IL-8) relative to MHA. However, in vivo delivery in a femoral artery ligation model showed enhanced cell retention in MHA hydrogels without improved vascular perfusion, underscoring the complex interplay between material chemistry, paracrine activity, and host response.