Topical Application of miR-200b-3p by Poloxamer 407-Based Hydrogel Accelerates Diabetic Wound Healing
Summary: This study evaluates the topical delivery of miR-200b-3p and miR-146a-5p mimics via poloxamer 407 hydrogel in a db/db mouse model of diabetic wounds, comparing efficacy against hydrogel alone or negative control. miR-200b-3p hydrogel significantly accelerated wound closure (71.5% reduction by day 14 vs. 32.8% for hydrogel), enhanced granulation thickness, and improved body weight maintenance. Mechanisms include downregulation of oxidative stress (Nox1/4, HO-1), inflammation (IL-6, IL-1β), senescence (OGT, p21, p53), and upregulation of collagen (Col1α2), alongside reduced macrophage infiltration (CD68) and increased angiogenesis (CD31). miR-200b-3p showed superior multilevel pro-healing effects over miR-146a-5p, suggesting its potential as an adjuvant for diabetic foot ulcers.
Key Highlights:
- miR-200b-3p hydrogel reduced wound area to 28.5% of baseline by day 14 (vs. 67.2% for hydrogel alone), with healing starting by day 6.
- Gene expression: Upregulated Col1α2 (1.553-fold); downregulated Nox1 (0.283-fold), IL-6 (0.255-fold), p21 (0.364-fold), and p53 (0.643-fold).
- Histology: Increased CD31 (1.993-fold) for angiogenesis; decreased CD68 (0.646-fold) for reduced inflammation in miR-200b-3p group.
- miR-200b-3p excelled in anti-ROS, anti-senescence (p53-dependent), and pro-angiogenic effects compared to miR-146a-5p.
- Topical application every 2 days proved feasible, with poloxamer 407 ensuring sustained release and biocompatibility.
Keywords:
miR-200b-3p,
poloxamer 407 hydrogel,
diabetic wound healing,
anti-senescence therapy,
wound healing innovation,
Wan-Yu Lo,
Cian-Huei Sin,
Huang-Joe Wang