Vascular Endothelial Growth Factor, Epidermal Growth Factor, and Epithelialization Analysis on Full-Thickness Wound Applied with Topical Erythropoietin
DOI:
https://doi.org/10.3889/oamjms.2022.8476Keywords:
Epidermal growth factor, Epithelialization rate, Medical care, Vascular endothelial growth factor, Wound healingAbstract
BACKGROUND: Skin wounds are a major challenge, such as full-thickness wounds that need a long time to heal. However, the addition of erythropoietin can accelerate the wound healing process.
AIM: This study was aimed to determine the effect of topical erythropoietin administration on vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and epithelialization in the wound healing process.
METHODS: This was randomized controlled trial. Full-thickness wounds were created on the back of each white rat. No treatment was administered in the control group (n=16), and topical erythropoietin was applied in the treatment group (n=16). The rats were euthanized on day 3 and day 6 post-surgery, respectively. The expression levels of VEGF, EGF, and microscopic epithelialization rate were examined.
RESULTS: The level of EGF expression in the treatment group increased significantly on day 3 by 2.84 times compared to the control group and on day 6 increased to 4.89 times compared to the control group (p < 0.001). The level of VEGF expression in the treatment group on day 3 increased 2.18 times compared to the control group and on day 6 increased to 2.65 times compared to the control group (p < 0.001). Meanwhile, epithelialization in the treatment group on day 3 increased 1.3 times compared to the control group and on day 6 increased up to 7.62 times compared to the control group (p < 0.001).
CONLUSION: Topical administration of erythropoietin could increase the expression of VEGF, EGF, and epithelialization in both early inflammatory and proliferative phases.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Sen CK. Human wound and its burden: Updated 2020 compendium of estimates. Adv Wound Care. 2021;10:281-92. https://doi.org/10.1089/wound.2021.0026 PMid:33733885
Veith AP, Henderson K, Spencer A, Sligar AD, Baker AB. Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev. 2019;146:97-125. https://doi.org/10.1016/j.addr.2018.09.010 PMid:30267742
Fuchs C, Pham L, Henderson J, Stalnaker KJ, Anderson RR, Tam J. Multi-faceted enhancement of full-thickness skin wound healing by treatment with autologous micro skin tissue columns. Sci Rep. 2021;11:1-13. https://doi.org/10.1038/s41598-021-81179-7 PMid:33462350
Mahmoudi M, Gould L. Opportunities and challenges of the management of chronic wounds: A multidisciplinary viewpoint. Chronic Wound Care Manag Res. 2020;7:27-36. https://doi.org/10.2147/cwcmr.s260136
Flood M, Weeks B, Anaeme KO, Aguirre H, Hobizal KB, Jiongco SE, et al. Treatment of deep full-thickness wounds containing exposed muscle, tendon, and/or bone using a bioactive human skin allograft: A large cohort case series. Wounds. 2020;32:164-73. PMid:32804658
Rivera AE, Spencer JM. Clinical aspects of full-thickness wound healing. Clin Dermatol. 2007;25:39-48. https://doi.org/10.1016/j.clindermatol.2006.10.001 PMid:17276200
Zeliadt N. Rita levi-montalcini: NGF, the prototypical growth factor. Proc Natl Acad Sci. 2013;110:4873-6. https://doi.org/10.1073/pnas.1302413110 PMid:23515326
Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease E-Book. 10th ed. Netherlands: Elsevier Health Sciences; 2020.
Brown GL, Curtsinger L 3rd, Brightwell JR, Ackerman DM, Tobin GR, Polk HC Jr., et al. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med. 1986;163:1319-24. https://doi.org/10.1084/jem.163.5.1319 PMid:3486247
Epstein JB, Gorsky M, Guglietta A, Le N, Sonis ST. The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy. Cancer. 2000;89:2258-65. https://doi.org/10.1002/1097-0142(20001201)89:11<2258:aid-cncr14>3.0.co;2-z PMid:11147596
Elliott S, Sinclair AM. The effect of erythropoietin on normal and neoplastic cells. Biologics. 2012;6:163-89. https://doi.org/10.2147/btt.s32281 PMid:22848149
Hamed S, Ullmann Y, Egozi D, Keren A, Daod E, Anis O, et al. Topical erythropoietin treatment accelerates the healing of cutaneous burn wounds in diabetic pigs through an aquaporin-3– dependent mechanism. Diabetes. 2017;66:2254-65. https://doi.org/10.2337/db16-1205 PMid:28546424
Siebert N, Xu W, Grambow E, Zechner D, Vollmar B. Erythropoietin improves skin wound healing and activates the TGF-β signaling pathway. Lab Investig. 2011;91:1753-65. https://doi.org/10.1038/labinvest.2011.125 PMid:21894148
Toleubayev M, Dmitriyeva M, Kozhakhmetov S, Igissinov N, Turebayev M, Omarbekov A, et al. Regenerative properties of recombinant human erythropoietin in the wound healing. Open Access Maced J Med Sci. 2021;9:113-7. https://doi.org/10.3889/oamjms.2021.5813
Hamed S, Ullmann Y, Masoud M, Hellou E, Khamaysi Z, Teot L. Topical erythropoietin promotes wound repair in diabetic rats. J Invest Dermatol. 2010;130:287-94. https://doi.org/10.1038/jid.2009.219 PMid:19626038
Galeano M, Altavilla D, Cucinotta D, Russo GT, Calò M, Bitto A, et al. Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse. Diabetes. 2004;53:2509-17. https://doi.org/10.2337/diabetes.53.9.2509 PMid:15331568
Galeano M, Altavilla D, Bitto A, Minutoli L, Calò M, Cascio PL, et al. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Crit Care Med. 2006;34:1139-46. https://doi.org/10.1097/01.ccm.0000206468.18653.ec PMid:16484928
Bader A, Lorenz K, Richter A, Scheffler K, Kern L, Ebert S, et al. Interactive role of trauma cytokines and erythropoietin and their therapeutic potential for acute and chronic wounds. Rejuvenation Res. 2011;14:57-66. https://doi.org/10.1089/rej.2010.1050 PMid:21329452
Yaghobee S, Rouzmeh N, Aslroosta H, Mahmoodi S, Khorsand A, Kharrazifard MJ. Effect of topical erythropoietin (EPO) on palatal wound healing subsequent to free gingival grafting (FGG). Braz Oral Res. 2018;32:e55. https://doi.org/10.1590/1807-3107bor-2018.vol32.0055 PMid:29898030
Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care. 2014;3:647-61. https://doi.org/10.1089/wound.2013.0517 PMid:25302139
Park JW, Hwang SR, Yoon IS. Advanced growth factor delivery systems in wound management and skin regeneration. Molecules. 2017;22:1-20. https://doi.org/10.3390/molecules22081259 PMid:28749427
Yamakawa S, Hayashida K. Advances in surgical applications of growth factors for wound healing. Burn Trauma. 2019;7:1-13. https://doi.org/10.1186/s41038-019-0148-1 PMid:30993143
Hong JP, Park SW. The combined effect of recombinant human epidermal growth factor and erythropoietin on full-thickness wound healing in diabetic rat model. Int Wound J. 2014;11:373-8. https://doi.org/10.1111/j.1742-481x.2012.01100.x PMid:23078553
Bretz CA, DIvoky V, Prchal J, Kunz E, Simmons AB, Wang H, et al. Erythropoietin signaling increases choroidal macrophages and cytokine expression, and exacerbates choroidal neovascularization. Sci Rep. 2018;8:1-12. https://doi.org/10.1038/s41598-018-20520-z PMid:29391474
Darmono S, Perdanakusuma DS, Nata’atmadja BS. Comparison of the total amount of macrophages on full thickness wound bed in the use of tulle, freeze-dried amnion, and microbial cellulose. Indian J Forensic Med Toxicol. 2020;14:1922-7. https://doi.org/10.37506/ijfmt.v14i2.3218
Nurmaulinda DS, Budi AS, Zarasade L, Utomo B. Epidermal growth factor (EGF) representing the role of other growth factors contained in platelet-rich plasma (PRP). Bali Med J. 2021;10:757-62. https://doi.org/10.15562/bmj.v10i2.2524
Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, et al. Epithelialization in wound healing: A comprehensive review. Adv Wound Care (New Rochelle). 2014;3:445-64. https://doi.org/10.1089/wound.2013.0473 PMid:25032064
Downloads
Published
How to Cite
License
Copyright (c) 2022 Noi Maya Anggrita Sari, Iswinarno Doso Saputro, Magda Rosalina Hutagalung (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
