Injectable Methylcellulose/Hyaluronic Acid/Collagen Hydrogel Loaded With Adipose-Derived Stem Cells Alleviates Skin Photoaging via Inhibition of HIF-1α: An in Vitro and in Vivo Study.

BACKGROUND: Adipose-derived stem cells (ADSCs) exhibit good anti-photoaging activity, yet inadequate homing numbers and low cell survival rates remain urgent challenges to overcome, and the underlying mechanisms are still unclear. METHODS: Methylcellulose (MC)/hyaluronic acid (HA)/Collagen I hydrogel (Gel) loaded with ADSCs (MHAC/ADSCs Gel) was prepared using the thermal dispersion method. Scanning electron microscopy was used to observe its microstructure, while swelling and degradation rates were determined by the pycnometer method. Subsequently, a photoaging HaCat cell model was established to evaluate the anti-photoaging potential of MHAC/ADSCs using the CCK-8 assay and Transwell experiment. Furthermore, qRT-PCR, WB, TargetScan bioinformatics analysis, and dual-luciferase reporter assays were conducted to investigate the underlying mechanisms of MHAC/ADSCs. Finally, a photoaging mouse model was established to assess the anti-photoaging activity of MHAC/ADSCs using H&E staining, Masson staining, immunohistochemistry, qRT-PCR, and WB. RESULTS: MHAC/ADSCs exhibited a 3D porous structure, remaining in a sol state at 20(°)C and forming a gel at 37(°)C. Additionally, it demonstrated excellent swelling properties and degradability. The results also revealed that MHAC/ADSCs showed significant anti-photoaging activity, promoting the migration of HaCat cells, increasing the expression of miR-18a and Collagen I, and inhibiting the expression of HIF-1α. In animal experiments, MHAC/ADSCs reversed epidermal thickening and collagen loss in mice and reduced the expression level of CD31. CONCLUSION: MHAC/ADSCs exhibit anti-photoaging activity by inhibiting the expression of HIF-1α through the upregulation of miR-18a, providing a promising approach for clinical treatment of photoaging.