The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells
Abstract
Chronic wounds in diabetes are common and serious health problems which also create significant economic burden in society. A comprehensive treatment has not yet been found in chronic wounds and new treatment recommendations are needed. The beneficial effects of metformin on wound healing was shown previously in healthy or diabetic animal models. Hyaluronic acid was also found to accelerate wound closure in clinical trials as well as animal models. Metformin and hyaluronic acid have been shown to be beneficial for wound healing in diabetes in in vivo studies, but their effect on wound healing under in vitro diabetic conditions have not yet been enlightened. In this study; we investigated the effects of metformin and hyaluronic acid on wound healing in mouse fibroblast cells under high glucose conditions. We used the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and scratch migration assays to examine fibroblast cell viability and migration in wound healing respectively. We showed that metformin and hyaluronic acid enhanced wound healing in fibroblasts incubated with high glucose by increasing cell viability, proliferation and migration. This is the first study to examine the effect of metformin, hyaluronic acid, or their combination on wound healing under high glucose conditions in vitro.
Keywords
References
- [1] Stephens P. Development of a cell-based diabetic wound assay. Altern Lab Anim. 2010; 38: 45-48. https://doi.org/10.1177/026119291003801S15
- [2] Spampinato SF, Caruso GI, De Pasquale R, Sortino MA, Merlo S. The treatment of impaired wound healing in diabetes: Looking among old drugs. Pharmaceuticals (Basel). 2020; 13(4): 60. https://doi.org/10.3390/ph13040060
- [3] Greenhalgh DG. Wound healing and diabetes mellitus. Clin Plast Surg. 2003; 30(1): 37-45. https://doi.org/10.1016/s0094-1298(02)00066-4
- [4] Pradhan L, Nabzdyk C, Andersen ND, LoGerfo FW, Veves A. Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Rev Mol Med. 2009; 11: e2. https://doi.org/10.1017/S1462399409000945
- [5] Dinh T, Elder S, Veves A. Delayed wound healing in diabetes: Considering future treatments. Diabetes Manage. 2011; 1 (5): 509-519. https://doi.org/10.2217/DMT.11.44.
- [6] Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017; 60(9): 1577-1585. https://doi.org/10.1007/s00125-017-4342-z
- [7] Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348 Pt 3(Pt 3):607-614.
- [8] Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011; 12(1): 21-35. https://doi.org/10.1038/nrm3025
Details
Primary Language
English
Subjects
Basic Pharmacology
Journal Section
Research Article
Publication Date
June 28, 2025
Submission Date
March 29, 2023
Acceptance Date
May 10, 2023
Published in Issue
Year 2023 Volume: 27 Number: 4
APA
Kazkayası, I., & Denizaltı, M. (2025). The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells. Journal of Research in Pharmacy, 27(4), 1338-1345. https://izlik.org/JA76TA48FC
AMA
1.Kazkayası I, Denizaltı M. The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells. J. Res. Pharm. 2025;27(4):1338-1345. https://izlik.org/JA76TA48FC
Chicago
Kazkayası, Inci, and Merve Denizaltı. 2025. “The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells”. Journal of Research in Pharmacy 27 (4): 1338-45. https://izlik.org/JA76TA48FC.
EndNote
Kazkayası I, Denizaltı M (July 1, 2025) The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells. Journal of Research in Pharmacy 27 4 1338–1345.
IEEE
[1]I. Kazkayası and M. Denizaltı, “The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells”, J. Res. Pharm., vol. 27, no. 4, pp. 1338–1345, July 2025, [Online]. Available: https://izlik.org/JA76TA48FC
ISNAD
Kazkayası, Inci - Denizaltı, Merve. “The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells”. Journal of Research in Pharmacy 27/4 (July 1, 2025): 1338-1345. https://izlik.org/JA76TA48FC.
JAMA
1.Kazkayası I, Denizaltı M. The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells. J. Res. Pharm. 2025;27:1338–1345.
MLA
Kazkayası, Inci, and Merve Denizaltı. “The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells”. Journal of Research in Pharmacy, vol. 27, no. 4, July 2025, pp. 1338-45, https://izlik.org/JA76TA48FC.
Vancouver
1.Inci Kazkayası, Merve Denizaltı. The Effects of Metformin and Hyaluronic Acid on Wound Healing in High Glucose Incubated Fibroblast Cells. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(4):1338-45. Available from: https://izlik.org/JA76TA48FC