The Effect of Topical Corticosteroid Time of Application on Fibroblast and Type III Collagen Expression in Oryctolagus cuniculus with Deep Dermal Burn Wound (As an Indicator for the Best Time to Start Topical Corticosteroid Application in Preventing Hypertrophic Scar)

Loelita Lumintang; I Made Suka Adnyana; Agus Roy Hamid; Hendra Sanjaya; Nyoman Golden; Putu Astawa; Made Darmajaya; I Wayan Juli Sumadi

doi:10.3889/oamjms.2021.6926

Authors

Loelita Lumintang Department of Surgery, Division of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia https://orcid.org/0000-0002-4802-0794
I Made Suka Adnyana Department of Surgery, Division of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
Agus Roy Hamid Department of Surgery, Division of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
Hendra Sanjaya Department of Surgery, Division of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
Nyoman Golden Department of Surgery, Neurosurgery Division, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
Putu Astawa Orthopedic and Traumatology Department, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
Made Darmajaya Department of Surgery, Pediatric Surgery Division, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Bali, Indonesia
I Wayan Juli Sumadi Department of Anatomical Pathology, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.6926

Keywords:

Deep dermal burn wound, Collagen type III, Fibroblast, Topical corticosteroid, Hypertrophic scar

Abstract

Background: Hypertrophic scar is an abnormal scar that causes physical deteriorations, psychological problems, and aesthetic issues. An excessive number of fibroblasts and collagen III expressions are histopathology indicators for the hypertrophic scar. The role of topical corticosteroids in suppressing inflammation and hypergranulation had widely demonstrated in previous studies. However, there is no study related to the application of topical corticosteroids as prevention of hypertrophic scars from burn wound found. Hence, this study aimed to examine the evidence of the effects of corticosteroid topical in decreasing the number of fibroblasts and type III collagen expression and the best time to start its application in preventing hypertrophic scars.

Methods: This randomized experimental post-test only study involved 54 deep dermal burn wounds on the ventral ear of female Oryctolagus cuniculus that distributed into three groups based on the healing phases. Each group consisted of treatments and controls. Corticosteroid topical application on the first treatment group (inflammatory phase group), the second group (proliferation phase group), and the third group (remodelling phase group) was started on day 3, on day 10, and day 21, respectively. Specimens taken on day 35. Haematoxylin-Eosin and Immunohistochemically staining performed to measure the number of fibroblasts and type III collagen and to observe the epithelization and inflammation process.

Results: The number of fibroblasts significantly decreased in the second treatment group (p =0.001) and followed by the first group (p = 0.016), but no significant decrease found in the third group (p = 0.430). The type III collagen decreased significantly in the second treatment group (p = 0.000) and followed by the third group (p = 0.019), but no significant decrease found in the first group. There was no statistically different number of fibroblast and type III collagen discovered between the controls. Complete epithelization found in all groups. Also, no ongoing inflammation found in all groups.

Conclusion : Topical corticosteroids on deep dermal burn wound revealed to be effective in reducing the number of fibroblasts and type III collagen with no healing disruption. The proliferation phase found to be the best time to start the application of topical corticosteroids.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Bigliardi PL. Specific stimulation of migration of human keratinocytes by muopiate receptor agonists. J Recept Signal Transduct Res. 2002;22(1-4):9-191. PMid:12503615 DOI: https://doi.org/10.1081/RRS-120014595

Akasaka Y. Basic fibroblast growth factor in an artificial dermis promotes apoptosis and inhibits expression of a-smooth muscle actin, leading to reduction of wound contraction. Wound Rep Regen. 2007;15(3):378-89. https://doi.org/10.1111/j.1524-475x.2007.00240.x PMid:17537125 DOI: https://doi.org/10.1111/j.1524-475X.2007.00240.x

Rook JM, McCarson KE. Delay of cutaneous wound closure by morphine via local blockade of peripheral tachykinin release. Biochem Pharmacol. 2007;74(5):7-752. https://doi.org/10.1016/j.bcp.2007.06.005 PMid:17632084 DOI: https://doi.org/10.1016/j.bcp.2007.06.005

Xie JL. Basic fibroblast growth factor (BFGF) alleviates the scar of the rabbit ear model in wound healing. Wound Rep Regen. 2008;16:576-81. https://doi.org/10.1111/j.1524-475x.2008.00405.x PMid:18638277 DOI: https://doi.org/10.1111/j.1524-475X.2008.00405.x

Tiede S. Basic fibroblast growth factor: A potential new therapeutic tool for the treatment of hypertrophic and keloid scars. Ann Anat. 2008;191:33-44. https://doi.org/10.1016/j.aanat.2008.10.001 PMid:19071002 DOI: https://doi.org/10.1016/j.aanat.2008.10.001

Rook JM. Morphine-induced early delays in wound closure: Involvement of sensory neuropeptides and modification of neurokinin receptor expression. Biochem Pharmacol. 2009;77(11):55-1747. https://doi.org/10.1016/j.bcp.2009.03.003 PMid:19428329 DOI: https://doi.org/10.1016/j.bcp.2009.03.003

Ogawa R, Akita S, Akaishi S, Aramaki-Hattori N, Dohi T, Hayashi T, et al. Diagnosis and treatment of keloids and hypertrophic scars-Japan scar workshop consensus document 2018. Burns Trauma. 2019;7:39. https://doi.org/10.1186/s41038-019-0175-y PMid:31890718 DOI: https://doi.org/10.1186/s41038-019-0175-y

Yoshino Y, Ohtsuka M. The wound/burn guidelines-6: Guidelines for the management of burns. J Dermatol. 2016;43(9):989-1010. PMid:26971391 DOI: https://doi.org/10.1111/1346-8138.13288

Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids. Plast Reconstr Surg. 2010;125(2):557-68. https://doi.org/10.1097/prs.0b013e3181c82dd5 PMid:20124841 DOI: https://doi.org/10.1097/PRS.0b013e3181c82dd5

Sandberg N. Time relationship between administration of cortisone and wound healing in rats. Acta Chir Scand. 1964;127:55-446. PMid:14169773

Fiuza C, Bustin M, Talwar S, Tropea M, Gerstenberger E, Shelhamer JH, et al. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood. 2003;101(7):2652-60. https://doi.org/10.1182/blood-2002-05-1300 PMid:12456506 DOI: https://doi.org/10.1182/blood-2002-05-1300

Friedrich EE. Thermal injury model in the rabbit ear with quantifiable burn progression and hypertrophic scar. Wound Repair Regen. 2017;25(2):327-37. https://doi.org/10.1111/wrr.12518 PMid:28370931 DOI: https://doi.org/10.1111/wrr.12518

Van den Broek LJ. Human hypertrophic and keloid scar models: Principles, limitations and future challenges from a tissue engineering perspective. Exp Dermatol. 2014;23(6):6-382. https://doi.org/10.1111/exd.12419 PMid:24750541 DOI: https://doi.org/10.1111/exd.12419

Domergue S, Jorgensen C, Noel D. Advances in research in animal models of burn-related hypertrophic scarring. J Burn Care Res. 2015;36(5):e259-66. https://doi.org/10.1097/bcr.0000000000000167 PMid:25356852 DOI: https://doi.org/10.1097/BCR.0000000000000167

Cuttle L. A porcine deep permal partial thickness burn model with hypertrophic scarring. Burns. 2006;32(7):20-806. https://doi.org/10.1016/j.burns.2006.02.023 PMid:16884856 DOI: https://doi.org/10.1016/j.burns.2006.02.023

Mace JE. Differential expression of the immunoinflammatory response in trauma patients: Burn vs. Non-burn. Burns. 2012;38(4):599-606. https://doi.org/10.1016/j.burns.2011.10.013 PMid:22103986 DOI: https://doi.org/10.1016/j.burns.2011.10.013

Goutos I, Ogawa R. Steroid tape: A promising adjunct to scar management. Scars Burns Heal. 2017;3:9-1. https://doi.org/10.1177/2059513117690937 DOI: https://doi.org/10.1177/2059513117690937

Mcshane D, Bellet J. Treatment of hypergranulation tissue with high potency topical corticosteroids in children. Pediatr Dermatol. 2012;29(5):675-8. https://doi.org/10.1111/j.1525-1470.2012.01724.x PMid:22612258 DOI: https://doi.org/10.1111/j.1525-1470.2012.01724.x

Shalom A, Wong L. Treatment of hypertrophic granulation tissue with topical steroids: 141. J Burn Care Res. 2003;24:S113. https://doi.org/10.1097/00004630-200303002-00141 DOI: https://doi.org/10.1097/00004630-200303002-00141

Hofman D. Use of topical corticosteroids on chronic leg ulcers. J Wound Care. 2007;16(5):227-230. https://doi.org/10.12968/jowc.2007.16.5.27047 PMid:17552408 DOI: https://doi.org/10.12968/jowc.2007.16.5.27047

Moio M. Treatment of hypergranulation tissue with intralesional injection of corticosteroids: Preliminary results. J Plast Reconstr Aesthet Surg. 2014;67(6):e167-8. https://doi.org/10.1016/j.bjps.2014.03.017 PMid:24725728 DOI: https://doi.org/10.1016/j.bjps.2014.03.017

Mandrea E. Topical diflorasone ointment for treatment of recalcitrant, excessive granulation tissue. Dermatol Surg. 1998;24(12):1409-10. https://doi.org/10.1111/j.1524-4725.1998.tb00024.x PMid:9865213 DOI: https://doi.org/10.1111/j.1524-4725.1998.tb00024.x

Arno AL. Up-to-date approach to manage keloids and hypertrophic scars: A useful guide. Burns. 2014;40(7):1255-66. https://doi.org/10.1016/j.burns.2014.02.011 PMid:24767715 DOI: https://doi.org/10.1016/j.burns.2014.02.011

Atiyeh BS. Nonsurgical management of hypertrophic scars: Evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast Surg. 2007;1:468-92. https://doi.org/10.1007/s00266-006-0253-y PMid:17576505 DOI: https://doi.org/10.1007/s00266-006-0253-y

Backdahl MS. The role of collagenase in wound healing. In: Collagenases. Texas: RG Landes Company; 1999. p. 207-20.

Perdanakusuma DS, Noer MS. Penanganan Parut Hipertrofi Dan Keloid. Surabaya: Airlangga University Press; 2006.

Oskeritzian CA. Mast cells and wound healing. Adv Wound Care (New Rochelle). 2006;1(1):23-8. https://doi.org/10.1089/wound.2011.0357 PMid:24527274 DOI: https://doi.org/10.1089/wound.2011.0357

Uva L. Mechanism of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018. https://doi.org/10.1155/2012/561018 PMid:23213332 DOI: https://doi.org/10.1155/2012/561018

Coondo A. Side-effect of tropical steroids: A long overdue revisit. Indian Dermatol Online J. 2014;5(4):416-25 https://doi.org/10.4103/2229-5178.142483 PMid:25396122 DOI: https://doi.org/10.4103/2229-5178.142483

Oishi Y. Molecular basis of the alteration in skin collagen metabolism in response to in vivo dexamethasone treatment: Effects on the synthesis of collagen Type I and III, collagenase, and tissue inhibitors of metalloproteinases. Br J Dermatol. 2002;147(5):58-868. https://doi.org/10.1046/j.1365-2133.2002.04949.x PMid:12410694 DOI: https://doi.org/10.1046/j.1365-2133.2002.04949.x

Verbruggen LA, Abe S. Glucocorticoids alter the ratio of Type III/Type I collagen synthesis by mouse dermal fibroblasts. Biochem Pharmacal. 1982;31:1711-5. https://doi.org/10.1016/0006-2952(82)90673-6 DOI: https://doi.org/10.1016/0006-2952(82)90673-6

Shull S. Glucocorticoids change the ratio of Type III to Type I procollagen extracellularly. Coll Relat Res. 1986;6(3):295-300. https://doi.org/10.1016/s0174-173x(86)80013-9 PMid:3769424 DOI: https://doi.org/10.1016/S0174-173X(86)80013-9

Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28(3):321-6. https://doi.org/10.1007/s00268-003-7397-6 PMid:14961191 DOI: https://doi.org/10.1007/s00268-003-7397-6

Broughton G. The basic science of wound healing. In: Barbul A, editor. Retraction of Witte. Plastic and Reconstructive Surgery. Vol. 77. United States: Lippincott Williams and Wilkins; 2006. p. 509-28.

Campos AC. Assessment and nutritional aspect of wound healing. Curr Opin Clin Nutr Metab Care. 2008;11(3):281-8. PMid:18403925

Todoroki T. From daily inquiry-adrenal corticosteroid. J Pract Pharm. 1988;39:1085-93.

Taheri A. Are corticosteroids effective for prevention of scar formation after second-degree skin burn? J Dermatol Treat. 2014;25(4):360-2. PMid:23688200 DOI: https://doi.org/10.3109/09546634.2013.806768

Pedersen JL. Topical glucocorticoid has no antinociceptive or anti-inflammatory effect in thermal injury. Br J Anaesth. 1994;72(4):379-82. https://doi.org/10.1093/bja/72.4.379 PMid:8155434 DOI: https://doi.org/10.1093/bja/72.4.379

Faurschou A. Topical corticosteroids in the treatment of acute sunburn a randomized, double-blind clinical trial. Arch Dermatol. 2008;144(5):620-4. https://doi.org/10.1001/archderm.144.5.620 PMid:18490588 DOI: https://doi.org/10.1001/archderm.144.5.620

Muramatsu T, Sekiguchi T. The clinical use of corticosteroid ointment for acute second degree burn. Jpn J Plast Surg. 1972;15:318.

Schulze S. Effect of prednisolone other systemic response and wound healing after colonic surgery. Arch Surg. 1997;132(2):129-35. https://doi.org/10.1001/archsurg.1997.01430260027005 PMid:9041914 DOI: https://doi.org/10.1001/archsurg.1997.01430260027005

Nicholson G. Perioperative steroid supplementation. Anaesthesia. 1998;53(11): 1091-104. PMid:10023279 DOI: https://doi.org/10.1046/j.1365-2044.1998.00578.x

Brown CJ, Buie WD. Perioperative stress dose steroids: Do they make a difference? J Am Coll Surg. 2001;193(6):678-86. PMid:11768685 DOI: https://doi.org/10.1016/S1072-7515(01)01052-3

Drake LA. Guidelines of care for the use of topical glucocorticosteroids. American academy of dermatology. J Am Acad Dermatol. 1996;35(4):615-9. https://doi.org/10.1016/s0190-9622(96)90690-8 PMid:8859293 DOI: https://doi.org/10.1016/S0190-9622(96)90690-8

Wang AS. Corticosteroids and wound healing: Clinical considerations in the perioperative period. Am J Surg. 2013;206(3):410-7. https://doi.org/10.12669/pjms.35.2.553 PMid:23759697 DOI: https://doi.org/10.1016/j.amjsurg.2012.11.018

Meseci E. Assessment of topical corticosteroid ointment on postcesarean scars prevention: A prospective clinical trial. Pak J Med Sci. 2019;35(2):309-14. PMid:31086506 DOI: https://doi.org/10.12669/pjms.35.2.553

Chowdri NA. Keloids and hypertrophic scars: Results with intraoperative and serial postoperative corticosteroid injection therapy. Aust N Z J Surg. 1999;69(9):9-655. https://doi.org/10.1046/j.1440-1622.1999.01658.x PMid:10515339 DOI: https://doi.org/10.1046/j.1440-1622.1999.01658.x

Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-29. https://doi.org/10.1177/0022034509359125 PMid:20139336 DOI: https://doi.org/10.1177/0022034509359125

Shih B. Molecular dissection of abnormal wound healing processes resulting in keloid disease. Wound Repair Regen. 2010;18(2):53-139. https://doi.org/10.1111/j.1524-475x.2009.00553.x PMid:20002895 DOI: https://doi.org/10.1111/j.1524-475X.2009.00553.x

Curran TA, Ghahary A. Evidence of a role for fibrocyte and keratinocyte-like cells in the formation of hypertrophic scars. J Burn Care Res. 2013;34(2):31-227. https://doi.org/10.1097/bcr.0b013e318254d1f9 PMid:22955158 DOI: https://doi.org/10.1097/BCR.0b013e318254d1f9

Tabas I, Glass CK. Anti-inflammatory therapy in chronic disease: Challenges and opportunities. Science. 2013;339(6116):166-72. https://doi.org/10.1126/science.1230720 PMid:23307734 DOI: https://doi.org/10.1126/science.1230720