Enhanced secretion of growth factors from ADSCs using an enzymatic antioxidant hydrogel in inflammatory environments and its therapeutic effect

Abstract

A catalytic ROS-scavenging hydrogel (HGel) was developed to enhance the growth factor secretion and the therapeutic efficacy of human adipose-derived stem cells (hADSCs) in inflammatory environments. The HGel is composed of heparin and hyaluronic acid, further functionalized with hemin to endow superoxide dismutase and catalase activities. The functionalization of hemin enables the HGel to effectively scavenge ROS (superoxide and H₂O₂), thereby protecting encapsulated hADSCs from oxidative stress and maintaining their metabolic activities. As a result, the HGel enhanced growth factor secretion of hADSCs in inflammatory conditions compared to non-functionalized, bare heparin/hyaluronic acid hydrogel (Gel). The therapeutic efficacy of the hADSC-encapsulated HGel (C/HGel) was evaluated in a diabetic wound model. The C/HGel significantly accelerated wound closure, reduced ROS levels, mitigated inflammation, and promoted angiogenesis compared to the hADSC-encapsulated Gel (C/Gel) as well as the HGel itself. The HGel has the potential to be utilized as an excellent cell carrier for stem cell therapy in various inflammatory diseases. Overall, this study demonstrated a strategy of enhancing growth factor secretion from stem cells using catalytic antioxidant hydrogels for superior regenerative effects in cell therapy.

Keywords: Diabetic wound healing; Hemin; Heparin; Hyaluronic acid; Hydrogel; ROS.