Original Article · Open access
Time-dependent effects of topical mucopolysaccharide polysulfate and silver sulfadiazine on wound healing in a rat excisional wound model
Abstract
Objectives: This study aims to evaluate the effects of topical creams containing mucopolysaccharide polysulfate (MPS) on wound healing using an experimental wound model.
Materials and methods: Standard full-thickness skin defects were created in 32 Wistar rats and monitored for 14 days under four different topical treatment protocols: Control (Group 1, n = 8), Hirudoid (Group 2, n = 8), Silverdin (Group 3, n = 8), and Hirudoid + Silverdin (Group 4, n = 8). Wound closure rates were quantified through photographic analysis, while histological and immunohistochemical healing characteristics were assessed using the Structure, Presence of Cells, Organization, and Tissue Integration (SPOT) score, additional histological indices, and the transforming growth factor-beta 1 (TGF-β1) H-score. Intergroup differences were analyzed using appropriate non-parametric statistical tests.
Results: On Day 3, wound closure rates were higher in the Hirudoid, Silverdin, and Hirudoid + Silverdin groups compared to the control group (p < 0.01). By Day 14, this difference sustained only in the Silverdin and Hirudoid + Silverdin groups, indicating that the early advantage observed with Hirudoid alone was not maintained over time (p < 0.01). No significant differences in the general histological parameters were observed among the groups (p > 0.05). However, the TGF-β1 H-score was lower in the Silverdin group than in the control and Hirudoid groups (p < 0.01).
Conclusion: Our study results suggest that MPS may accelerate early wound closure, but does not significantly improve wound closure in later stages, and its combination with silver sulfadiazine offers no additional benefit compared to silver sulfadiazine alone.
Declarations
Author Contributions
S.S., Z.K.: Data curation; F.D.: Formal analysis, visualization; R.D.: Funding acquisition, writing-original draft; Y.B., M.Y.: Investigation; R.D., M.T.: Methodology; M.A., S.S.: Project administration; Z.K.: Software; M.Y.: Supervision; Y.B.: Validation; M.A., M.Y.: Writing-review & editing.
Conflict of Interest
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
Financial Disclosure
The authors received no financial support for the research and/or authorship of this article.
Data Sharing Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
AI Disclosure
The authors declare that artificial intelligence (AI) tools were not used, or were used solely for language editing, and had no role in data analysis, interpretation, or the formulation of conclusions. All scientific content, data interpretation, and conclusions are the sole responsibility of the authors. The authors further confirm that AI tools were not used to generate, fabricate, or ‘hallucinate’ references, and that all references have been carefully verified for accuracy.
References
- Loo HL, Goh BH, Lee LH, Chuah LH. Application of chitosan-based nanoparticles in skin wound healing. Asian J Pharm Sci 2022;17:299-332. DOI: 10.1016/j.ajps.2022.04.001.
- Gheibi N, Samiee-Rad F, Sofiabadi M, Mosayebi E, Shalbaf Z. The effect of combining humic and fulvic acids poultice on wound healing in male rats. J Cutan Aesthet Surg 2024;17:105-11. DOI: 10.4103/JCAS.JCAS_92_23.
- Yavuz Veizi BG, Güven Ş, Demir C, Erdoğan Y, Veizi E, Fırat A. The role of preoperative nutritional status in predicting surgical outcomes after total knee arthroplasty: A CONUT-based analysis. Jt Dis Relat Surg 2025;36:604-11. DOI: 10.52312/jdrs.2025.2412.
- Fujiwara-Sumiyoshi S, Ueda Y, Fujikawa M, Osaki M, Yamanaka N, Matsumoto T. Mucopolysaccharide polysulfate promotes microvascular stabilization and barrier integrity of dermal microvascular endothelial cells via activation of the angiopoietin-1/Tie2 pathway. J Dermatol Sci 2021;103:25- 32. DOI: 10.1016/j.jdermsci.2021.05.008.
- Kurachi T, Ishimaru H, Tadakuma R, Okaue M, Koda A, Ueda Y, et al. Mucopolysaccharide polysulfate increases local skin blood volume through nitric oxide production. J Dermatol Sci 2024;114:133-40. DOI: 10.1016/j.jdermsci.2024.05.001.
- Masson-Meyers DS, Andrade TAM, Caetano GF, Guimaraes FR, Leite MN, Leite SN, et al. Experimental models and methods for cutaneous wound healing assessment. Int J Exp Pathol 2020;101:21-37. DOI: 10.1111/iep.12346.
- Turhan B, Sağlam S, Yücel MO, Dalaslan RE, Sungur MA, Demir F, et al. Comparison of topical hypericum perforatum and metformin effectiveness in wound healing in streptozotocin-induced diabetic rats. Front Endocrinol (Lausanne) 2025;16:1691294. DOI: 10.3389/fendo.2025.1691294.
- van de Vyver M, Boodhoo K, Frazier T, Hamel K, Kopcewicz M, Levi B, et al. Histology scoring system for murine cutaneous wounds. Stem Cells Dev 2021;30:1141-52. DOI: 10.1089/scd.2021.0124.
- Çalıskan E, Gamsızkan M, Açıkgöz G, Durmuş M, Toklu S, Doğrul A, et al. Intralesional treatments for hypertrophic scars: Comparison among corticosteroid, 5-fluorouracil and botulinum toxin in rabbit ear hypertrophic scar model. Eur Rev Med Pharmacol Sci 2016;20:1603-8.
- Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep 2017;7:16878. DOI: 10.1038/s41598-017-17204-5.
- Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET, et al. ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinformatics 2017;18:529. DOI: 10.1186/s12859-017-1934-z.
- Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF-β family in wound healing, burns and scarring: A review. Int J Burns Trauma 2012;2:18-28.
- McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS Sr. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 1985;109:716-21.
- Zhang Q, Zhou Y, Chen L, Xu Y. Therapeutic effect of mucopolysaccharide polysulfate cream in prevention of postoperative scars. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2018;43:293-300. DOI: 10.11817/j.issn.1672-7347.2018.03.010.
- Li H. Clinical effect of mucopolysaccharide polysulfate cream combined with SD-Ag cream on deep partial thickness burning. Med J Wuhan Univ 2012;33:571-3.
- Livaoğlu M, Kerimoğlu S, Sönmez B, Livaoğlu A, Karaçal N. The effect of Hirudoid on random skin-flap survival in rats. J Plast Reconstr Aesthet Surg 2010;63:1047-51. DOI: 10.1016/j.bjps.2009.03.018.
- Kuisma I, Tamelander G. Mucopolysaccharide polysulphate cream in the prevention of pressure sores--a double blind study. Ann Clin Res 1987;19:374-7.
- Görög P, Raake W. Antithrombotic effect of a mucopolysaccharide polysulfate after systemic, topical and percutaneous application. Arzneimittelforschung 1987;37:342-5.
- Wanitphakdeedecha R, Eimpunth S, Manuskiatti W. The effects of mucopolysaccharide polysulphate on hydration and elasticity of human skin. Dermatol Res Pract 2011;2011:807906. DOI: 10.1155/2011/807906.
- Hoppensteadt DA, Fareed J, Raake P, Raake W. Endogenous release of tissue factor pathway inhibitor by topical application of an ointment containing mucopolysaccharide polysulfate to nonhuman primates. Thromb Res 2001;103:157-63. DOI: 10.1016/s0049-3848(01)00280-8.