Sodium alginate/gelatin hydrogels loaded with adipose‐derived mesenchymal stem cells promote wound healing in diabetic rats

Abstract Background Chronic refractory wounds are a common complication in diabetic patients. Adipose‐derived mesenchymal stem cells (ASCs) have been shown to play an essential role in diabetic wound repair. Aims To determine whether a composite of ASCs and sodium alginate/gelatin (Gel‐Al) hydrogel can promote diabetic wound healing. Methods Full‐thickness cutaneous wounds were created in streptozotocin‐induced diabetic rats prior to treatment with Gel‐Al hydrogels loaded with ASCs. Hydrogel biocompatibility and wound healing were analyzed. Hematoxylin and eosin staining, Masson staining, immunofluorescence, enzyme‐linked immunosorbent assays (ELISA), and quantitative real‐time PCR were performed for the assessment of cellular responses. Results Compared to the control group or Gel‐Al alone group, the combination of Gel‐Al and ASCs promoted wound closure, facilitated granulation tissue regeneration and collagen deposition, and upregulated the expression of vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), epidermal growth factor (EGF), and endothelial cell marker CD31. Moreover, the combination of Gel‐Al and ASCs decreased interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) expression, increased transforming growth factor beta1 (TGFβ1), interleukin‐10 (IL‐10), interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13) expression, and increased M2 macrophage polarization. Conclusions Gel‐Al hydrogels loaded with ASCs accelerate diabetic wound healing. The Gel‐Al hydrogel‐based ASC system therefore represents an innovative therapeutic strategy for diabetic wound repair.