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A Review on Wound Healing: Pathophysiology, Animal Model and Role of Biomarkers

Shivani sharma, Sagarika Majhi, Dr. Meenakshi Sharma



Blood cells, extracellular matrix, parenchyma cells, and soluble mediators are all involved in the physiological process of wound healing, which is highly complex, dynamic, interactive, and well-regulated. The 4 stages of wound healing are separated out. Hemostasis b. Inflammation c. Proliferation d. Remodeling. Many animal models are employed in the examination of wound healing activities because a large variety of models have been produced for examining different components of the repair response. Skin wound healing and the efficiency of different treatment regimens have been studied extensively using rats and mice. Biomarkers are being discovered using biomaterials derived locally from human wounds, as well as high-throughput "omics" modalities (genomic, proteomic, lipidomic, and metabolomic analyses). In this review, we discuss the current status of clinically applicable biomarkers and propose multiple steps in the validation and implementation process, including those measured in tissue specimens, such as -catenin and c-myc, wound fluid, matrix metalloproteinases and interleukins, swabs, wound microbiota, and serum, such as procalcitonin and matrix metalloproteinases.

Keywords: Wound healing, inflammation, Biomarkers, Animal Model

Citation: Shivani Sharma, Sagarika Majhi, Meenakshi Sharma. A Review on Wound Healing: Pathophysiology, Animal Model and Role of Biomarkers. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2022; 9(3): 23–33p.

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Wysocki AB. Wound fluids and the pathogenesis of chronic wounds. Journal of WOCN. 1996 Nov 1; 23(6): 283–90.

Serra MB, Barroso WA, Silva NN, Silva SD, Borges AC, Abreu IC, Borges MO. From inflammation to current and alternative therapies involved in wound healing. International journal of inflammation. 2017 Oct; 2017.

Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. Journal of clinical oncology. 2009 Nov 11; 27(31): 5287.

Gautam MK, Purohit V, Agarwal M, Singh A, Goel RK. In vivo healing potential of Aegle marmelos in excision, incision, and dead space wound models. The Scientific World Journal. 2014 Mar 4; 2014.

Kayapınar M, Seyhan N, Avunduk MC, Savaci N. Saving the zone of stasis in burns with melatonin: an experimental study in rats. Turkish Journal of Trauma and Emergency Surgery. 2015 Nov 1; 21(6): 419–24.

Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clinics in dermatology. 2007 Jan 1; 25(1):9–18.

Malviya N, Jain S. Wound healing activity of aqueous extract of Radix paeoniae root. Acta Pol Pharm. 2009 Sep 1; 66(5): 543–7.

Broughton II. G., Janis, JE, Attinger, CE, 2006. The basic science of wound healing. Plast. Reconstr. Surg.; 117 (7 Suppl).

Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, Chan RK, Christy RJ. & Chung, KK (2015). Burn wound healing and treatment: review and advancements. Critical Care.; 19(1): 1.

Heggers JP, Kucukcelebi A, Listengarten D, Stabenau J, Ko F, Broemeling LD, Robson MC, Winters WD. Beneficial effect of Aloe on wound healing in an excisional wound model. The Journal of Alternative and Complementary Medicine. 1996 Jun 1; 2(2): 271–7.

Witte MB, Barbul A. General principles of wound healing. Surgical Clinics of North America. 1997 Jun 1; 77(3): 509-28.

Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. Journal of international medical research. 2009 Oct; 37(5): 1528–42.

Nayak BS, Kanhai J, Milne DM, Pereira LP, Swanston WH. Experimental evaluation of ethanolic extract of Carapa guianensis L. leaf for its wound healing activity using three wound models. Evidence-Based Complementary and Alternative Medicine. 2011 Jan 1; 2011.

Patil MV, Kandhare AD, Bhise SD. Pharmacological evaluation of ethanolic extract of Daucus carota Linn root formulated cream on wound healing using excision and incision wound model. Asian Pacific Journal of Tropical Biomedicine. 2012 Feb 1; 2(2): S646–55.

Kumar VK, Khan AA, Nagarajan K. Animal models for the evaluation of wound healing activity. Int. Bull. Drug Res. 2013; 3(5): 93–107.

Lawrence WT. Physiology of the acute wound. Clinics in plastic surgery. 1998 Jul 1; 25(3): 321–40.

Cañedo-Dorantes L, Cañedo-Ayala M. Skin acute wound healing: a comprehensive review. International journal of inflammation. 2019 Oct; 2019.

Reynolds B, Richards JB, Horn K, Karraker K. Delay discounting and probability discounting as related to cigarette smoking status in adults. Behavioural processes. 2004 Jan 30; 65(1):


Grada A, Mervis J, Falanga V. Research techniques made simple: animal models of wound healing. Journal of Investigative Dermatology. 2018 Oct 1; 138(10): 2095–105.

Agarwal PK, Singh A, Gaurav K, Goel S, Khanna HD, Goel RK. Evaluation of wound healing activity of extracts of plantain banana (Musa sapientum var. paradisiaca) in rats. Indian Journal of Experimental Biology. 2009 January; 47(01): 32–40.

Chien S, Wilhelmi BJ. A simplified technique for producing an ischemic wound model. JoVE (Journal of Visualized Experiments). 2012 May 2(63): e3341.

DeOliveira D, Jiao Y, Ross JR, Corbin K, Xiao Q, Toncheva G, Anderson-Evans C, Yoshizumi TT, Chen BJ, Chao NJ. An ear punch model for studying the effect of radiation on wound healing. International journal of radiation biology. 2011 Aug 1; 87(8):869–77.

Nwomeh BC, Yager DR, Cohen IK. Physiology of the chronic wound. Clinics in plastic surgery. 1998 Jul 1; 25(3): 341–56.

Beshir K, Shibeshi W, Ejigu A, Engidawork E. In-vivo wound healing activity of 70% ethanol leaf extract of Beciumgrandiflorum Lam.(Lamiaceae) in mice. Ethiopian Pharmarmaceutical Journal. 2016; 32: 117–30.

Patel S, Maheshwari A, Chandra A. Biomarkers for wound healing and their evaluation. Journal of wound care. 2016 Jan 2; 25(1): 46–55.

Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997 Apr 4; 276(5309): 75–81.

Hunt TK, Hopf H, Hussain Z. Physiology of wound healing. Advances in skin & wound care. 2000 May 1; 13: 6.

Henry G, Garner WL. Inflammatory mediators in wound healing. Surgical Clinics. 2003 Jun 1; 83(3): 483–507.

Pawar RS, Chaurasiya PK, Rajak H, Singour PK, Toppo FA, Jain A. Wound healing activity of Sida cordifolia Linn. in rats. Indian journal of pharmacology. 2013 Sep; 45(5): 474.

George B, Jeffrey EJ. Wound healing: An overview. J Plast Reconstr Surg. 1976; 117: 1.

Adzick NS. The molecular and cellular biology of wound repair. Annals of Surgery. 1997 Feb; 225(2): 236.

Agyare C, Osafo N, Boakye YD. Biomarkers of Wound Healing. Wound Healing-Current Perspectives. 2019 May 10.

Nguyen TT, Mobashery S, Chang M. Roles of matrix metalloproteinases in cutaneous wound healing. Wound healing-new insights into ancient challenges. 2016 Oct 12: 37–71.

Chhabra S, Chhabra N, Kaur A, Gupta N. Wound healing concepts in clinical practice of OMFS. Journal of Maxillofacial and Oral Surgery. 2017 Dec; 16(4): 403–23.

Colwell AS, Krummel TM, Longaker MT, Lorenz HP. An in vivo mouse excisional wound model of scarless healing. Plastic and reconstructive surgery. 2006 Jun 1; 117(7): 2292–6.

Karppinen SM, Heljasvaara R, Gullberg D, Tasanen K, Pihlajaniemi T. Toward understanding scarless skin wound healing and pathological scarring. F1000Research. 2019; 8.

Lindley LE, Stojadinovic O, Pastar I, Tomic-Canic M. Biology and biomarkers for wound healing. Plastic and reconstructive surgery. 2016 Sep; 138(3): 18S.

Monaco JL, Lawrence WT. Acute wound healing: an overview. Clinics in plastic surgery. 2003 Jan 1; 30(1): 1–2.

Nayak BS, Kanhai J, Milne DM, Swanston WH, Mayers S, Eversley M, Rao AC. Investigation of the wound healing activity of Carapa guianensis L.(Meliaceae) bark extract in rats using excision, incision, and dead space wound models. Journal of Medicinal Food. 2010 Oct 1; 13(5): 1141–6.

Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: a cellular perspective. Physiological reviews. 2019 Jan 1;99(1):665-706.

Schreml S. R. m. Szeimies, L. Prantl, S. Karrer, M. Landthaler, P. Babilas. Oxygen in acute and chronic wound healing. Br J Dermatol. Br. J. Dermatol. 2010; 163: 257.

Tejada S, Manayi A, Daglia M, F Nabavi S, Sureda A, Hajheydari Z, Gortzi O, Pazoki-Toroudi H, M Nabavi S. Wound healing effects of curcumin: A short review. Current pharmaceutical biotechnology. 2016 Sep 1; 17(11): 1002–7.


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