Comparison of the effects of two different wound dressing materials on wound healing in mucosal defects created in diabetic and healthy rats
DOI:
https://doi.org/10.1590/1678-7765-2026-0096Keywords:
Wound healing, Wound dressing, Diabetes mellitus, RatsAbstract
Introduction Diabetes mellitus impairs oral mucosal wound healing by prolonging inflammation and disrupting angiogenesis and growth factor regulation. Aim To evaluate the effects of Ora-Aid (TBM Corporation, Gwangju, Republic of Korea) and cyanoacrylate (GluStitch, City of Industry, CA, USA) on palatal wound healing in diabetic and healthy rats. Methodology A total of 146 male Wistar albino rats were used: 144 were divided into six groups: control (C), cyanoacrylate (CY), Ora-Aid (OA), diabetes (D), diabetes+cyanoacrylate (DCY), and diabetes+Ora-Aid (DOA) (n=24 each; 8 per time point), and 2 served as baseline controls. Diabetes was induced by intraperitoneal streptozotocin (STZ; Santa Cruz Biotechnology, Texas, USA) at 60 mg/kg. A 4-mm palatal excisional wound was created. Wound area was measured from photographs using ImageJ v1.54g (Wayne Rasband, National Institutes of Health, USA). Immunohistochemical analyses assessed vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-10, and tumor necrosis factor-alpha. Data were analyzed using the Kruskal-Wallis test and Bonferroni-adjusted Mann-Whitney U tests. Statistical significance was evaluated based on adjusted p-values, with p<0.05 considered significant. Results In healthy rats, wound areas after cyanoacrylate and Ora-Aid were similar to controls. In diabetic rats, both wound dressings reduced wound area, particularly on day 14 [median (IQR): D, 0.33 (0.82); DCY, 0.27 (0.71); DOA, 0.09 (0.09); D vs DCY, p=0.037; D vs DOA, p=0.002]. Immunohistochemical analyses showed that Ora-Aid more pronouncedly affected VEGF expression in healthy groups and FGF expression in diabetic groups, whereas cyanoacrylate showed time-dependent effects on growth factors and inflammatory markers. Conclusion Ora-Aid and cyanoacrylate positively influenced oral mucosal wound healing under diabetic conditions. Ora-Aid more prominently supported the VEGF-related angiogenic response under healthy conditions and FGF-related fibroblastic activity under diabetic conditions, whereas cyanoacrylate showed time-dependent regulatory effects on growth factors and the inflammatory response.
Downloads
References
1- Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585-601. doi: 10.1111/j.1524-475X.2008.00410.x
» https://doi.org/10.1111/j.1524-475X.2008.00410.x
2- Wang PH, Huang BS, Horng HC, Yeh CC, Chen YJ. Wound healing. J Chin Med Assoc. 2018;81(2):94-101. doi: 10.1016/j.jcma.2017.11.002
» https://doi.org/10.1016/j.jcma.2017.11.002
3- Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009;37(5):1528-42. doi: 10.1177/147323000903700531
» https://doi.org/10.1177/147323000903700531
4- Rodriguez AB, Alhachache S, Velasquez D, Chan HL. A systematic review of oral wound healing indices. PLoS One. 2024;19(2):e0290050. doi: 10.1371/journal.pone.0290050
» https://doi.org/10.1371/journal.pone.0290050
5- Shi Z, Yao C, Shui Y, Li S, Yan H. Research progress on the mechanism of angiogenesis in wound repair and regeneration. Front Physiol. 2023;14:1284981. doi: 10.3389/fphys.2023.1284981
» https://doi.org/10.3389/fphys.2023.1284981
6- Pan Q, Fan R, Chen R, Yuan J, Chen S, Cheng B. Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration. Front Bioeng Biotechnol. 2023;11:1150819. doi: 10.3389/fbioe.2023.1150819
» https://doi.org/10.3389/fbioe.2023.1150819
7- Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol. 2008;15(3):215-20. doi: 10.1097/MOH.0b013e3282f97d98
» https://doi.org/10.1097/MOH.0b013e3282f97d98
8- Takaya K, Aramaki-Hattori N, Sakai S, Okabe K, Asou T, Kishi K. Fibroblast growth factor 7 suppresses fibrosis and promotes epithelialization during wound healing in mouse fetuses. Int J Mol Sci. 2022;23(13):7087. doi: 10.3390/ijms23137087
» https://doi.org/10.3390/ijms23137087
9- Xiao T, Yan Z, Xiao S, Xia Y. Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization. Stem Cell Res Ther. 2020;11:232. doi:10.1186/s13287-020-01755-y
» https://doi.org/10.1186/s13287-020-01755-y
10- Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765. doi: 10.1146/annurev.immunol.19.1.683
» https://doi.org/10.1146/annurev.immunol.19.1.683
11- Abiko Y, Selimovic D. The mechanism of protracted wound healing on oral mucosa in diabetes. Bosn J Basic Med Sci. 2010;10(3):186-91. doi: 10.17305/bjbms.2010.2683
» https://doi.org/10.17305/bjbms.2010.2683
12- Lang X, Li L, Li Y, Feng X. Effect of diabetes on wound healing: a bibliometrics and visual analysis. J Multidiscip Healthc. 2024;17:1275-89. doi: 10.2147/JMDH.S457498
» https://doi.org/10.2147/JMDH.S457498
13- Xue C, Chen K, Gao Z, Bao T, Dong L, Zhao L, et al. Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction. Cell Commun Signal. 2023;21(1):298. doi: 10.1186/s12964-022-01016-w
» https://doi.org/10.1186/s12964-022-01016-w
14- Gomes CC, Guimarães LS, Pinto LC, Camargo GA, Valente MI, Sarquis MI. Investigations of the prevalence and virulence of Candida albicans in periodontal and endodontic lesions in diabetic and normoglycemic patients. J Appl Oral Sci. 2017;25(3):274-81. doi: 10.1590/1678-7757-2016-0432
» https://doi.org/10.1590/1678-7757-2016-0432
15- Shaik RA, Alotaibi MF, Nasrullah MZ, Alrabia MW, Asfour HZ, Abdel-Naim AB. Cordycepin-melittin nanoconjugate intensifies wound healing efficacy in diabetic rats. Saudi Pharm J. 2023;31(5):736-45. doi: 10.1016/j.jsps.2023.03.014
» https://doi.org/10.1016/j.jsps.2023.03.014
16- Ko KI, Sculean A, Graves DT. Diabetic wound healing in soft and hard oral tissues. Transl Res. 2021;236:72-86. doi: 10.1016/j.trsl.2021.05.001
» https://doi.org/10.1016/j.trsl.2021.05.001
17- Brizeno LA, Assreuy AM, Alves AP, Sousa FB, Silva PG, Sousa SC, et al. Delayed healing of oral mucosa in a diabetic rat model: implication of TNF-a, IL-1ß and FGF-2. Life Sci. 2016;155:36-47. doi: 10.1016/j.lfs.2016.04.033
» https://doi.org/10.1016/j.lfs.2016.04.033
18- Tavelli L, Barootchi S, Stefanini M, Zucchelli G, Giannobile WV, Wang HL. Wound healing dynamics, morbidity, and complications of palatal soft-tissue harvesting. Periodontol 2000. 2023;92(1):90-119. doi: 10.1111/prd.12466
» https://doi.org/10.1111/prd.12466
19- Sinha S, Naik M, Wright V, Timmons J, Campbell AC. A single-blind randomized trial comparing n-butyl-2-cyanoacrylate and sutures for skin closure in hand surgery. J Hand Surg Br. 2001;26(3):264-5. doi: 10.1054/jhsb.2000.0572
» https://doi.org/10.1054/jhsb.2000.0572
20- Tavelli L, Ravidà A, Saleh MHA, Maska B, Suárez-López Del Amo F, Rasperini G, et al. Pain perception following epithelialized gingival graft harvesting: a randomized clinical trial. Clin Oral Investig. 2019;23(1):459-68. doi: 10.1007/s00784-018-2455-5
» https://doi.org/10.1007/s00784-018-2455-5
21- Min HS, Kang DY, Lee SJ, Yun SY, Park JC, Cho IW. Effect of attachable periodontal wound dressing on postoperative pain and healing. J Dent Rehabil Appl Sci. 2020;36(1):21-8. doi: 10.14368/jdras.2020.36.1.21
» https://doi.org/10.14368/jdras.2020.36.1.21
22- Sun J, Chen T, Zhao B, Fan W, Shen Y, Wei H, et al. Acceleration of oral wound healing under diabetes mellitus conditions using bioadhesive hydrogel. ACS Appl Mater Interfaces. 2023;15(1):416-31. doi: 10.1021/acsami.2c17424
» https://doi.org/10.1021/acsami.2c17424
23- Niki E. Lipid oxidation that is, and is not, inhibited by vitamin E: consideration about physiological functions of vitamin E. Free Radic Biol Med. 2021;176:1-15. doi: 10.1016/j.freeradbiomed.2021.09.001
» https://doi.org/10.1016/j.freeradbiomed.2021.09.001
24- Rodrigues PA, Paramashivaiah R, Prabhuji MLV, Azevedo RG. Optimized healing of the donor wound area with Ora-Aid containing polymers and vitamin E: a case series. RGUHS J Dent Sci. 2022;14(1):42-6.
25- Lee JH, Lee KE, Kang SW, Park SH, Chae YK, Lee MH, et al. Effect of orodispersible hyaluronic acid film on palatal mucosa wound healing. Oral Dis. 2024;30:518-27. doi: 10.1111/odi.14517
» https://doi.org/10.1111/odi.14517
26- Çalisir M, Akpinar A, Talmaç AC, Lektemur Alpan A, Göze ÖF. Humic acid enhances wound healing in the rat palate. Evid Based Complement Alternat Med. 2018;2018:1783513. doi: 10.1155/2018/1783513
» https://doi.org/10.1155/2018/1783513
27- Albayrak SC, Dural S, Ates Özdemir D, Usubütün A, Çetinkaya MA, Basol Göksülük M. A comparative experimental study of healing effect of different oral wound dressings for oral ulcers. Cumhuriyet Dent J. 2026;29(1):111-21. doi: 10.7126/cumudj.1794805
» https://doi.org/10.7126/cumudj.1794805
28- Kang S, Jang EJ, Jo HM, Kang SS, Lee MS, Yun SY, et al. Effects of a topically applied oral wound dressing film on intra-oral wound healing in rabbits. In Vivo. 2022;36(4):1745-52. doi: 10.21873/invivo.12887
» https://doi.org/10.21873/invivo.12887
29- Zhu T, Park HC, Son KM, Yang HC. Effects of dimethyloxalylglycine on wound healing of palatal mucosa in a rat model. BMC Oral Health. 2015;15:60. doi: 10.1186/s12903-015-0047-1
» https://doi.org/10.1186/s12903-015-0047-1
30- Gül M, Günay A, Tanik A. Effects of caffeic acid phenethyl ester and ankaferd blood stopper on secondary wound healing of oral mucosal tissue. Turk J Med Sci. 2020;50:248-57. doi: 10.3906/sag-1908-114
» https://doi.org/10.3906/sag-1908-114
31- Assar DH, Elhabashi N, Mokhbatly AAA, Abdel-Sattar E, Abdel-Hamid M, Hassan HS, et al. Wound healing potential of licorice extract in a rat model. Biomed Pharmacother. 2021;143:112151. doi: 10.1016/j.biopha.2021.112151
» https://doi.org/10.1016/j.biopha.2021.112151
32- Liu Y, Liu Y, Deng J, Li W, Nie X. Fibroblast growth factor in diabetic foot ulcer: progress and therapeutic prospects. Front Endocrinol (Lausanne). 2021;12:744868. doi: 10.3389/fendo.2021.744868
» https://doi.org/10.3389/fendo.2021.744868
33- Mahmoud NN, Hamad K, Al Shibitini A, Juma S, Sharifi S, Gould L, et al. Investigating inflammatory markers in wound healing: understanding implications and identifying artifacts. ACS Pharmacol Transl Sci. 2024;7(1):18-27. doi: 10.1021/acsptsci.3c00336
» https://doi.org/10.1021/acsptsci.3c00336
34- Hedayatyanfard K, Bagheri Khoulenjani S, Abdollahifar MA, Amani D, Habibi B, Zare F, et al. Chitosan/PVA/doxycycline film and nanofiber accelerate diabetic wound healing in rats. Iran J Pharm Res. 2020;19:225-39. doi: 10.22037/ijpr.2020.112620.13859
» https://doi.org/10.22037/ijpr.2020.112620.13859
35- Saraiva M, Vieira P, O'Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med. 2020;217(1):e20190418. doi: 10.1084/jem.20190418
» https://doi.org/10.1084/jem.20190418
36- Aravinthan A, Park JK, Hossain MA, Sharmila J, Kim HJ, Kang CW, et al. Collagen-based sponge hastens wound healing via decrease of inflammatory cytokines. 3 Biotech. 2018;8:487. doi: 10.1007/s13205-018-1497-3
Downloads
Published
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
Todo o conteúdo do periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons do tipo atribuição CC-BY.