Healing potential of chitosan PVA hydrogels on excised wound in diabetic albino mice
DOI:
https://doi.org/10.2478/AMB-2024-0061Keywords:
APTES, chitosan/PVA hydrogels, skin grafting, type I diabetes, wound healingAbstract
Objective. This study aimed to evaluate the efficiency of the developed chitosan/polyvinyl alcohol (CS/PVA) hydrogel crosslinked with 3-aminopropyltriethoxysilane (APTES) for its wound healing potential on diabetic wounds in mice models. Methods. A total of 18 Swiss albino mice were randomly assigned into a control and five treatment groups (CP0, CP50, CP100, CP200, and CP300) based on APTES crosslinker concentrations. After a 13-14 hour fast, an injection of alloxan monohydrate was used to induce type I diabetes. Mice
were anesthetized, followed by the creation of a 6 mm dorsal wound using a biopsy punch. Throughout trial, wound size was measured and photographed, and blood glucose levels were monitored. Results. On day 15, treated groups showed complete wound healing, while the control group was in transitional stage of healing. After therapy, mice were euthanized and blood, skin, graft, kidney, and liver samples were taken for biochemical and histological investigation. Skin graft histology showed complete epithelialization and granulation in all treatment groups compared to controls. CP300 had most skin regeneration. Inflammation and necrosis were observed in the control group. Liver and kidney histological sections showed structural changes, but hydrogel induced minimal toxicity to the organs. The reported effects may have been caused by diabetes rather than hydrogels. Biochemical analysis of liver enzymes exhibited a significant (p < 0.05) increase in bilirubin, alkaline phosphate (ALP), alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, suggesting liver dysfunction. Kidney function tests showed no significant difference in urea and creatinine concentrations. Conclusion. The CP300 hydrogel demonstrated an excellent healing response and is recommended as a suitable material for wound dressing.
References
Abed Shlaka W, Saeed SR. Gold and silver nanoparticles with modified chitosan/PVA: synthesis, study the toxicity and anticancer activity. Nanomedicine Research Journal, 2023;8(3), 231-245.
Ahmadi F, Oveisi Z, Samani SM, Amoozgar Z. Chitosan based hydrogels: characteristics and pharmaceutical applications. Research in pharmaceutical sciences, 2015;10(1), 1.
Amin MA, Abdel-Raheem IT. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats. Archives of pharmacal research, 2014;37, 1016-1031.
Ara C, Jabeen S, Afshan G et al. Angiogenic potential and wound healing efficacy of chitosan derived hydrogels at varied concentrations of APTES in chick and mouse models. International journal of biological macromolecules, 2022;202, 177-190.
Aswathy S, Narendrakumar U, Manjubala I. Commercial hydrogels for biomedical applications. Heliyon, 2020;6(4).
Ayele AG, Kumar P, Engidawork E. Antihyperglycemic and hypoglycemic activities of the aqueous leaf extract of Ru-bus Erlangeri Engl (Rosacea) in mice. Metabolism Open, 2021;11, 100118.
Azab AK, Kleinstern J, Doviner V et al. Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of 131I-norcholesterol. Journal of controlled release, 2007;123(2), 116-122.
Azevedo E. Chitosan hydrogels for drug delivery and tissue engineering applications. Int J Pharm Pharm Sci, 2015;7(12), 8-14.
Belhekar S, Chaudhari P, Saryawanshi J et al. Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp extracts on alloxan-induced diabetic rats. Indian Journal of Pharmaceutical Sciences, 2013;75(2), 217.
Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Advanced drug delivery reviews, 2010;62(1), 83-99.
Bundgaard CJ, Kalliokoski O, Abelson KS, Hau J. Acclimatization of mice to different cage types and social groupings with respect to fecal secretion of IgA and corticosterone metabolites. in vivo, 2012;26(6), 883-888.
Cao H, Duan L, Zhang Y et al. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal transduction and targeted therapy, 2021;6(1), 426.
Chen G, He L, Zhang P et al. Encapsulation of green tea polyphenol nanospheres in PVA/alginate hydrogel for promoting wound healing of diabetic rats by regulating PI3K/AKT pathway. Materials Science and Engineering: C, 2020;110, 110686.
de Melo CL, Queiroz MGR, Fonseca SG et al. Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet. Chemico-biological interactions, 2010;185(1), 59-65.
Dunn JS, Kirkpatrick J, McLetchie N, Telfer S. Necrosis of the islets of Langerhans produced experimentally. Journal of Pathology and Bacteriology, 1943;55, 245-257.
Elviri L, Asadzadeh M, Cucinelli R et al. Macroporous chitosan hydrogels: Effects of sulfur on the loading and release behaviour of amino acid-based compounds. Carbohydrate Polymers, 2015;132, 50-58.
Falanga V. Wound healing and its impairment in the diabetic foot. The Lancet, 2005;366(9498), 1736-1743.
Goldner MG, & Gomori G. Alloxan diabetes in the dog. Endocrinology, 1943;33(5), 297-308.
Ho T-C, Chang C-C, Chan H-P et al. Hydrogels: Properties and applications in biomedicine. Molecules, 2022;27(9), 2902.
Huang C-Y, Hu K-H, Wei Z-H. Comparison of cell behavior on pva/pva-gelatin electrospun nanofibers with random and aligned configuration. Scientific Reports, 2016;6(1), 37960.
İnal M, Mülazımoğlu G. Production and characterization of bactericidal wound dressing material based on gelatin nanofiber. International journal of biological macromolecules, 2019;137, 392-404.
Ketema T, Yohannes M, Alemayehu E, Ambelu A. Evaluation of immunomodulatory activities of methanolic extract of khat (Catha edulis, Forsk) and cathinone in Swiss albino mice. BMC immunology, 2015;16, 1-11.
Kim J-Y, Jun J-H, Kim S-J et al. Wound healing efficacy of a chitosan-based film-forming gel containing tyrothricin in various rat wound models. Archives of pharmacal research, 2015;38, 229-238.
Kittur F, Prashanth KH, Sankar KU, Tharanathan R. Characterization of chitin, chitosan and their carboxymethyl derivatives by differential scanning calorimetry. Carbohydrate Polymers, 2002;49(2), 185-193.
Lenzen S, Panten U. Alloxan: history and mechanism of action. Diabetologia, 1988;31, 337-342.
Lenzen S, Tiedge M, Jörns A, Munday R. Alloxan derivatives as a tool for the elucidation of the mechanism of the diabetogenic action of alloxan. Lessons from Animal Diabetes VI: 75th Anniversary of the Insulin Discovery, 1996;113-122.
Liu H, Wang C, Li C et al. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC advances, 2018;8(14), 7533-7549.
Lotfy M, Adeghate J, Kalasz H et al. Chronic complications of diabetes mellitus: a mini review. Current diabetes reviews, 2017;13(1), 3-10.
Muyenga T. The effect of Kigelia africana fruit extract on blood glucose in diabetes induced mice The University of Zambia] 2015.
Muzzarelli R, Muzzarelli C. Chitosan chemistry: relevance to the biomedical sciences. Polysaccharides I: structure, characterization and use, 2005;151-209.
Nagarajan S, Radhakrishnan S, Kalkura SN et al. Overview of protein-based biopolymers for biomedical application. Macromolecular Chemistry and Physics, 2019;220(14), 1900126.
Nosrati H, Aramideh Khouy R, Nosrati A et al. Nanocomposite scaffolds for accelerating chronic wound healing by enhancing
angiogenesis. Journal of Nanobiotechnology, 2021;19(1), 1-21.
Peschke E, Ebelt H, Brömme H-J, Peschke D. ‘Classical’and ‘new’diabetogens – comparison of their effects on isolated rat pancreatic islets in vitro. Cellular and Molecular Life Sciences CMLS, 2000;57, 158-164.
Qiao Y, Sun J, Xia S et al. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food & function, 2014;5(6), 1241-1249.
Qin Y, Xing R, Liu S et al. Novel thiosemicarbazone chitosan derivatives: Preparation, characterization, and antifungal activity. Carbohydrate Polymers, 2012;87(4), 2664-2670.
Ranmadugala D, Ebrahiminezhad A, Manley-Harris M et al. Impact of 3–aminopropyltriethoxysilane-coated iron oxide
nanoparticles on menaquinone-7 production using B. subtilis. Nanomaterials, 2017;7(11), 350.
Rezvanian M, Ng S-F, Alavi T, Ahmad W. In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic
wound healing in Streptozotocin-induced diabetic rats. International journal of biological macromolecules, 2021;171, 308-319.
Rhea L, Dunnwald M. Murine excisional wound healing model and histological morphometric wound analysis. JoVE (Journal
of Visualized Experiments) 2020(162), e61616.
Ribeiro MP, Espiga A, Silva D et al. Development of a new chitosan hydrogel for wound dressing. Wound repair and regeneration, 2009;17(6), 817-824.
Rodrigues M, Kosaric N, Bonham CA et al. Wound healing: a cellular perspective. Physiological reviews, 2019;99(1), 665-706.
Rohilla A, Ali S. Alloxan induced diabetes: mechanisms and effects. International journal of research in pharmaceutical and biomedical sciences, 2012;3(2), 819-823.
Shariatinia Z. Pharmaceutical applications of chitosan. Advances in colloid and interface science, 2019;263, 131-194.
Shaw TJ, Martin P. Wound repair at a glance. Journal of cell science, 2009;122(18), 3209-3213.
Singh A, Narvi S, Dutta P, Pandey N. External stimuli response on a novel chitosan hydrogel crosslinked with formaldehyde. Bulletin of Materials Science, 2006;29, 233-238.
Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological research, 2001;50(6), 537-546.
Thanou M, Verhoef J, Junginger H. Oral drug absorption enhancement by chitosan and its derivatives. Advanced drug delivery reviews, 2001;52(2), 117-126.
Tracy LE, Minasian RA, Caterson E. Extracellular matrix and dermal fibroblast function in the healing wound. Advances in wound care, 2016;5(3), 119-136.
Van Pelt L. Ketamine and xylazine for surgical anesthesia in rats. Journal of the American Veterinary Medical Association, 1977;171(9), 842-844.
Vedadghavami A, Minooei F, Mohammadi MH et al. Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications. Acta biomaterialia, 2017;62, 42-63.
Wang X, Ge J, Tredget EE, Wu Y. The mouse excisional wound splinting model, including applications for stem cell transplantation. Nature protocols, 2013;8(2), 302-309.
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