Comparative regenerative mechanisms of adipose-derived mesenchymal stem cell- and conditioned medium-loaded three-dimensional bioprinted hydrogels in chronic diabetic wounds.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Chronic diabetic wounds remain a major clinical challenge owing to impaired angiogenesis, persistent inflammation and cellular dysfunction. In this study, we developed a bioadhesive composite hydrogel scaffold (gelatin methacryloyl/alginate methacrylate [GA]) fabricated using digital light processing three-dimensional (3D) bioprinting, in which human adipose-derived mesenchymal stem cells (ADSCs) or their conditioned medium (CM) was incorporated to generate 3D skin constructs, and compared the paracrine effects on skin regeneration. We characterized the microstructures of GA-ADSC and GA-CM scaffolds; profiled CM proteins and systematically compared the effects of GA-ADSCs and GA-CM on fibroblast proliferation, migration, angiogenesis and macrophage polarization in vitro . Their therapeutic efficacy was further evaluated in diabetic mouse wound models, including analyses of collagen deposition, angiogenesis and fibrosis markers. Furthermore, proteomic analysis was performed to understand the underlying mechanisms. In vitro , both GA-ADSCs and GA-CM promoted fibroblast proliferation, migration, angiogenesis and macrophage M2 polarization. Moreover, they accelerated wound closure in diabetic mice by enhancing collagen deposition and neovascularization (CD31) and suppressing α-smooth muscle actin and transforming growth factor-β1 expression. Notably, GA-ADSCs showed prolonged cell

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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