Wound healing with minimal scarring remains a critical challenge in clinical practice. Scarring can impair both the function and appearance of healed tissues, which is particularly concerning in skin wounds.
Fibrosis, a primary cause of scarring, is often exacerbated by chronic inflammation. Metformin, widely known for its anti-inflammatory and anti-fibrotic properties through the activation of AMPK, has been shown to enhance wound healing in previous studies. However, oral administration of metformin can lead to adverse systemic effects.
Researchers explored a novel approach of administering metformin topically through a metformin lotion (ML) formulation aimed at improving healing outcomes while minimizing scarring.
Materials and Methods
Researchers used full-thickness skin wound models in rats to evaluate the therapeutic efficacy of a 6% metformin lotion (ML). Two groups were established: one receiving the 6% ML and another receiving a control lotion (0% ML). Key markers of inflammation, fibrosis, and tissue regeneration were assessed using ELISA and immunostaining. Markers studied included HMGB1, IL-1β, TGF-β1, α-SMA (alpha smooth muscle actin), collagen I, collagen III, and phosphorylated AMPK (p-AMPK). They focused on analyzing the differences in tissue structure, inflammatory response, and fibrotic tissue formation between the two groups.
Key Findings
1. Wound Healing and Tissue Regeneration
- Accelerated Healing: 6% ML-treated wounds healed faster with tissue resembling normal skin, while control wounds formed scar-like tissue.
- Improved Skin Structure: The ML-treated group showed better tissue regeneration with minimal scarring.
2. Anti-inflammatory Effects
- Reduced Inflammation: The 6% ML significantly lowered inflammatory markers (HMGB1, IL-1β), indicating a strong anti-inflammatory response.
- Inhibition of HMGB1 Release: Immunostaining revealed that ML prevented the release of HMGB1 into the tissue, reducing inflammation.
3. Anti-fibrotic Effects
- Decreased TGF-β1 and α-SMA+ Cells: ML treatment reduced fibrosis by lowering TGF-β1 and α-SMA+ myofibroblast presence, which are key in scar formation.
- Modulated Collagen Levels: ML decreased collagen III (associated with scarring) while increasing collagen I (linked to healthy skin).
4. AMPK Activation
- Increased p-AMPK Activity: ML-treated wounds showed enhanced p-AMPK, known for its role in reducing fibrosis and inflammation.
- Metformin’s Fibrosis Reduction: The study confirmed metformin’s anti-fibrotic mechanism via AMPK activation in skin wound healing.
This study introduces a promising metformin-based lotion (6% ML) that shows substantial potential for scarless skin wound healing. By combining anti-inflammatory and anti-fibrotic effects with localized delivery, 6% ML accelerates healing, reduces scar formation, and enhances the regeneration of normal skin tissue.
Future research should focus on clinical trials to validate these findings and explore broader applications, such as in chronic wounds and surgical sites. Given its minimal systemic side effects and the ease of application, this metformin lotion could significantly advance wound care management, offering a novel therapeutic approach for both patients and clinicians.
*Please consult with your healthcare provider for further information
Link to the study: https://tinyurl.com/cvcepa6h
