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DOI: 10.1055/s-0042-1744429
Therapeutic Effects of Amnion-Conjugated Chitosan-Alginate Membranes on Diabetic Wounds in an Induced Diabetic Swine Model: An In Vitro and In Vivo Study
Funding This work was supported by a research-promoting grant from Keimyung University Dongsan Medical Center, in 2013.
Abstract
Background Chitosan (CS) is a well-known antimicrobial dressing material. Moreover, widely used amniotic membranes contain growth factors beneficial for wound healing. Herein, we created a novel amnion-conjugated CS-alginate membrane dressing and tested its wound healing potency in a diabetic swine model.
Methods The bovine amniotic powder growth factor contents were evaluated by protein assay, and the powder's wound healing effects were assessed in vitro by HaCaT cell scratch closure. In vivo, two minipigs developed streptozotocin-induced diabetes. Serial serum glucose measurements and intravenous glucose tolerance tests were performed to confirm their diabetic status. Twelve square-shaped wounds created on each pig's back were randomly divided into control (n = 4), CS (n = 4), and amnion-CS (AC; n = 4) groups and treated accordingly with different dressings. Wound healing in each group was assessed by measuring wound contraction over time, capturing wound perfusion with indocyanine green (ICG) angiography, and histologically analyzing inflammatory markers.
Results Amniotic powder elution promoted HaCaT cell migration in the scratch wound model, suggesting its beneficial in vitro wound healing effects. In vivo, the CS and AC groups showed earlier wound contraction initiation and reepithelialization and earlier wound perfusion improvement by ICG angiography than the control group. Additionally, the wound size of the AC group at week 3 was significantly smaller than those in the control group. There was no significant difference in the numbers of acute and chronic inflammatory cells between the groups.
Conclusion The amnion-conjugated CS-alginate membrane, as well as CS dressing alone, could be a favorable dressing option for diabetic wounds.
Author Contributions
W.J. conceived the study, performed the experiments, provided the experimental design, analyzed the data, and wrote the manuscript. J.H. conceived the study, analyzed the data, edited figures, and wrote part of the manuscript. M.J. designed and manufactured the experimental materials. M.J. and S.A. performed the animal experiments and analyzed the data of wound perfusion. T.J. wrote part of the manuscript. S.K. performed and analyzed the histologic experiments and revised the manuscript. D.S. provided the concept of the experiment, analyzed the data, and wrote the manuscript.
Ethical Approval
The animal experiments in the study were approved by the Institutional Animal Care and Use Committee (DGMIF-16102001–00).
Prior Presentation
This study was presented at PRS KOREA 2020 held online on November 13, 2020.
Publikationsverlauf
Artikel online veröffentlicht:
06. April 2022
© 2022. The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Saeedi P, Petersohn I, Salpea P. et al; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843
- 2 Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet 2005; 366 (9498): 1719-1724
- 3 Hosseinnejad M, Jafari SM. Evaluation of different factors affecting antimicrobial properties of chitosan. Int J Biol Macromol 2016; 85: 467-475
- 4 Singh R, Shitiz K, Singh A. Chitin and chitosan: biopolymers for wound management. Int Wound J 2017; 14 (06) 1276-1289
- 5 Bischoff M, Stachon T, Seitz B. et al. Growth factor and interleukin concentrations in amniotic membrane-conditioned medium. Curr Eye Res 2017; 42 (02) 174-180
- 6 Qi M, Zhou Q, Zeng W. et al. Growth factors in the pathogenesis of diabetic foot ulcers. Front Biosci 2018; 23: 310-317
- 7 Grüssner R, Nakhleh R, Grüssner A, Tomadze G, Diem P, Sutherland D. Streptozotocin-induced diabetes mellitus in pigs. Horm Metab Res 1993; 25 (04) 199-203
- 8 Bae JE, Kim CK, Kim SP, Yang EK, Kim IS. Process development of a virally-safe acellular bovine amniotic membrane for biological dressing. Microbiol Biotechnol Lett. 2010; 38 (04) 420-427
- 9 Mesa MG, Duarte HÁ, Carretero JH, López MM, Vilas MM. De Marco Formula effectiveness as an adjunctive therapy to prevent infected ischemic diabetic foot amputation and reduce plasma fibrinogen. J Tissue Viability 2011; 20 (02) 67-72
- 10 van Battum P, Schaper N, Prompers L. et al. Differences in minor amputation rate in diabetic foot disease throughout Europe are in part explained by differences in disease severity at presentation. Diabet Med 2011; 28 (02) 199-205
- 11 Lipsky BA. Medical treatment of diabetic foot infections. Clin Infect Dis 2004; 39 (Suppl. 02) S104-S114
- 12 Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther 2014; 31 (08) 817-836
- 13 Sahana TG, Rekha PD. Biopolymers: applications in wound healing and skin tissue engineering. Mol Biol Rep 2018; 45 (06) 2857-2867
- 14 Mo X, Cen J, Gibson E, Wang R, Percival SL. An open multicenter comparative randomized clinical study on chitosan. Wound Repair Regen 2015; 23 (04) 518-524
- 15 Totsuka Sutto SE, Rodríguez Roldan YI, Cardona Muñoz EG. et al. Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: a double-blind, randomized, clinical trial. Diab Vasc Dis Res 2018; 15 (04) 348-351
- 16 Zhang ZY, Yang J, Fan ZH. et al. Fresh human amniotic membrane effectively promotes the repair of injured common peroneal nerve. Neural Regen Res 2019; 14 (12) 2199-2208
- 17 Eslani M, Baradaran-Rafii A, Cheung AY, Djalilian AR, Holland EJ. Amniotic membrane transplantation in acute severe ocular chemical injury: a randomized clinical trial. Am J Ophthalmol 2019; 205: 203
- 18 Ilic D, Vicovac L, Nikolic M, Lazic Ilic E. Human amniotic membrane grafts in therapy of chronic non-healing wounds. Br Med Bull 2016; 117 (01) 59-67
- 19 Adly OA, Moghazy AM, Abbas AH, Ellabban AM, Ali OS, Mohamed BA. Assessment of amniotic and polyurethane membrane dressings in the treatment of burns. Burns 2010; 36 (05) 703-710
- 20 Koizumi NJ, Inatomi TJ, Sotozono CJ, Fullwood NJ, Quantock AJ, Kinoshita S. Growth factor mRNA and protein in preserved human amniotic membrane. Curr Eye Res 2000; 20 (03) 173-177
- 21 Park M, Kim S, Kim IS, Son D. Healing of a porcine burn wound dressed with human and bovine amniotic membranes. Wound Repair Regen 2008; 16 (04) 520-528
- 22 Min S, Yoon JY, Park SY, Kwon HH, Suh DH. Clinical effect of bovine amniotic membrane and hydrocolloid on wound by laser treatment: prospective comparative randomized clinical trial. Wound Repair Regen 2014; 22 (02) 212-219
- 23 Momeni M, Zarehaghighi M, Hajimiri M. et al. In vitro and in vivo investigation of a novel amniotic-based chitosan dressing for wound healing. Wound Repair Regen 2018; 26 (01) 87-101
- 24 Seaton M, Hocking A, Gibran NS. Porcine models of cutaneous wound healing. ILAR J 2015; 56 (01) 127-138