Conclusions
Our findings suggest that the ADSC-loaded β-ChNF hydrogel activated the HIF-1α/MMP9 axis through AldoA feedback to promote diabetic wound healing.
Methods
We prepared the ADSC-loaded β-ChNF hydrogel to repair wounds of db/db diabetic mice. Wound healing rate, histopathology, enzyme-linked immunosorbent assay, and western blot were used to confirm its role and mechanism in promoting diabetic wound healing.
Results
The ADSC-loaded β-ChNF hydrogel accelerated wound healing in db/db diabetic mice, as indicated by increased cell proliferation, epithelization, and tissue granulation in the skin. Moreover, expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), matrix metalloproteinase 9 (MMP9), and TIMP metallopeptidase inhibitor 1 (TIMP1) were upregulated. These results demonstrate the beneficial effects of this ADSC-loaded β-ChNF hydrogel on diabetic wound healing. Furthermore, we show that the ADSC-loaded β-ChNF hydrogel activated aldolase A (AldoA)/hypoxia-inducible factor 1α (HIF-1α) signaling. An inhibitor of HIF-1α markedly decreased the promotive effects of the ADSC-loaded β-ChNF hydrogel on wound healing and reduced expression of VEGF, VEGFR, MMP9, and TIMP1. Conclusions: Our findings suggest that the ADSC-loaded β-ChNF hydrogel activated the HIF-1α/MMP9 axis through AldoA feedback to promote diabetic wound healing.