Year 2021 Vol. 29 No 4




Grodno State Medical University, Grodno,
The Republic of Belarus

The creation and implementation of new methods of study and local wound care occur in stages: in vitro, in vivo and clinical trials. The fundamental point of this process is to study the effect of the proposed agent on the experimental wound healing models of laboratory animals taking into consideration the common healing phases of course and similarity of animal wound healing with human one. At the initial stage the main problems faced by the researcher include the selection of the optimal experimental animal, while animal models are suitable for many skin disorders. The lack of strong evidence and relevant guidelines regarding the most appropriate form of local-wound care in literature and the fragmentation of the available information lead to the fact that during the development of the experiment, the scientists spend time, resources and operate on an additional number of animals. This article summarizes the literature data on the applied modeling methods as for the most common and rare types of skin wounds including burns and trophic ulcers in various laboratory animals. Those who prepared the experiment should have paid closer attention to the features of creating such wounds and nuances so as the proven techniques of their creation in various species are shown. Variants of the course and prospects for the development of this area of surgery are presented.

Keywords: animals, disease models, wound healing, skin injuries, burns, laboratory, ulcer
p. 480-489 of the original issue
  1. Singh S, Young A, McNaught CE. The physiology of wound healing. Surgery. 2017;35(9):473-77. doi: 10.1016/j.mpsur.2017.06.004
  2. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014 Dec 3;6(265):265sr6. doi: 10.1126/scitranslmed.3009337
  3. Ansell DM, Holden KA, Hardman MJ. Animal models of wound repair: Are they cutting it? Exp Dermatol. 2012 Aug;21(8):581-85. doi: 10.1111/j.1600-0625.2012.01540.x
  4. Nunan R, Harding KG, Martin P. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Dis Model Mech. 2014 Nov;7(11):1205-13. doi: 10.1242/dmm.016782
  5. Spear M. Acute or chronic? Whats the difference? Plast Surg Nurs. 2013 Apr-Jun;33(2):98-100. doi: 10.1097/PSN.0b013e3182965e94
  6. Davidson JM. Animal models for wound repair. Arch Dermatol Res. 1998 Jul;290(Suppl):S1-11. doi: 10.1007/PL00007448
  7. Shrivastav A, Mishra AK, Ali SS, Ahmad A, Abuzinadah MF, Khan NA. In vivo models for assesment of wound healing potential: a systematic review. Wound Medicine. 2018 Mar;20:43-53. doi: 10.1016/j.wndm.2018.01.003
  8. Kieran I, Knock A, Bush J, So K, Metcalfe A, Hobson R, Mason T, OKane S, Ferguson M. Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies. Wound Repair Regen. 2013 May-Jun;21(3):428-36. doi: 10.1111/wrr.12043
  9. Charoenkwan K, Iheozor-Ejiofor Z, Rerkasem K, Matovinovic E. Scalpel versus electrosurgery for major abdominal incisions. Cochrane Database Syst Rev. 2017 Jun 14;6(6):CD005987. doi: 10.1002/14651858.CD005987.pub3
  10. Yang Q, Phillips PL, Sampson EM, Progulske-Fox A, Jin S, Antonelli P, Schultz GS. Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Wound Repair Regen. 2013 Sep-Oct;21(5):704-14. doi: 10.1111/wrr.12074
  11. Chen L, Nagaraja S, Zhou J, Zhao Y, Fine D, Mitrophanov AY, Reifman J, DiPietro LA. Wound healing in Mac-1 deficient mice. Wound Repair Regen. 2017 May;25(3):366-76. doi: 10.1111/wrr.12531
  12. Ashcroft GS, Horan MA, Ferguson MW. The effects of ageing on wound healing: immunolocalisation of growth factors and their receptors in a murine incisional model. J Anat. 1997 Apr;190(Pt 3):351-65. doi: 10.1046/j.1469-7580.1997.19030351.x
  13. Routley CE, Ashcroft GS. Effect of estrogen and progesterone on macrophage activation during wound healing. Wound Repair Regen. 2009 Jan-Feb;17(1):42-50. doi: 10.1111/j.1524-475X.2008.00440.x
  14. Kiwanuka E, Hackl F, Philip J, Caterson EJ, Junker JP, Eriksson E. Comparison of healing parameters in porcine full-thickness wounds transplanted with skin micrografts, split-thickness skin grafts, and cultured keratinocytes. J Am Coll Surg. 2011 Dec;213(6):728-35. doi: 10.1016/j.jamcollsurg.2011.08.020
  15. Jabeen S, Clough ECS, Thomlinson AM, Chadwick SL, Ferguson MWJ, Shah M. Partial thickness wound: Does mechanism of injury influence healing? Burns. 2019 May;45(3):531-42. doi: 10.1016/j.burns.2018.08.010
  16. Barillo DJ, Croutch CR, Barillo AR, Reid F, Singer A. Safety evaluation of silver-ion dressings in a porcine model of deep dermal wounds: A GLP study. Toxicol Lett. 2020 Feb 1;319:111-18. doi: 10.1016/j.toxlet.2019.10.023
  17. Vasilkov AYu, Dovnar RI, Smotryn SM, Iaskevich NN, Naumkin AV. Healing of experimental aseptic skin wound under the influence of the wound dressing, containing silver nanoparticles. Am J Nanotechnol Nanomed. 2018;1(2):69-77.
  18. Davis SC, Mertz PM, Eaglstein WH. Second-degree burn healing: the effect of occlusive dressings and a cream. J Surg Res. 1990 Mar;48(3):245-48. doi: 10.1016/0022-4804(90)90220-v
  19. Boykin JV, Eriksson E, Pittman RN. In vivo microcirculation of a scald burn and the progression of postburn dermal ischemia. Plast Reconstr Surg. 1980 Aug;66(2):191-98. doi: 10.1097/00006534-198008000-00002
  20. Walker HL, Mason AD Jr. A standard animal burn. J Trauma. 1968 Nov;8(6):1049-51. doi: 10.1097/00005373-196811000-00006
  21. Nguyen PK, Smith AL, Reynolds KJ. A literature review of different pressure ulcer models from 19422005 and the development of an ideal animal model. Australas Phys Eng Sci Med. 2008 Sep;31(3):223-25. doi: 10.1007/bf03179348
  22. Grada A, Mervis J, Falanga V. Research Techniques Made Simple: Animal Models of Wound Healing. J Invest Dermatol. 2018 Oct;138(10):2095-2105.e1. doi: 10.1016/j.jid.2018.08.005
  23. Reid RR, Sull AC, Mogford JE, Roy N, Mustoe TA. A novel murine model of cyclical cutaneous ischemia-reperfusion injury. J Surg Res. 2004 Jan;116(1):172-80. doi: 10.1016/s0022-4804(03)00227-0
  24. Wassermann E, van Griensven M, Gstaltner K, Oehlinger W, Schrei K, Redl H. A chronic pressure ulcer model in the nude mouse. Wound Repair Regen. 2009 Jul-Aug;17(4):480-84. doi: 10.1111/j.1524-475X.2009.00502.x
  25. Sundin BM, Hussein MA, Glasofer S, El-Falaky MH, Abdel-Aleem SM, Sachse RE, Klitzman B. The role of allopurinol and deferoxamine in preventing pressure ulcers in pigs. Plast Reconstr Surg. 2000 Apr;105(4):1408-21. doi: 10.1097/00006534-200004040-00021
  26. Fang RC, Mustoe TA. Animal models of wound healing: utility in transgenic mice. J Biomater Sci Polym Ed. 2008;19(8):989-1005. doi: 10.1163/156856208784909327
  27. Roy S, Biswas S, Khanna S, Gordillo G, Bergdall V, Green J, Marsh CB, Gould LJ, Sen CK. Characterization of a preclinical model of chronic ischemic wound. Physiol Genomics. 2009 May 13;37(3):211-24. doi: 10.1152/physiolgenomics.90362.2008
  28. Chen C, Schultz GS, Bloch M, Edwards PD, Tebes S, Mast BA. Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds. Wound Repair Regen. 1999 Nov-Dec;7(6):486-94. doi: 10.1046/j.1524-475x.1999.00486.x
  29. Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak AM, Swaim SF, Vangilder J, Lee-Ambrose L, Martin FG. The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Vet Surg. 2003 Nov-Dec;32(6):515-23. doi: 10.1111/j.1532-950x.2003.00515.x
  30. Sisco M, Mustoe TA. Animal models of ischemic wound healing. Toward an approximation of human chronic cutaneous ulcers in rabbit and rat. Methods Mol Med. 2003;78:55-65. doi: 10.1385/1-59259-332-1:055
  31. Ahn ST, Mustoe TA. Effects of ischemia on ulcer wound healing: a new model in the rabbit ear. Ann Plast Surg. 1990 Jan;24(1):17-23. doi: 10.1097/00000637-199001000-00004
  32. King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012 Jun;166(3):877-94. doi: 10.1111/j.1476-5381.2012.01911.x
  33. Wagner JD, Cline JM, Shadoan MK, Bullock BC, Rankin SE, Cefalu WT. Naturally occurring and experimental diabetes in cynomolgus monkeys: a comparison of carbohydrate and lipid metabolism and islet pathology. Toxicol Pathol. 2001 Jan-Feb;29(1):142-48. doi: 10.1080/019262301301418955
  34. Velander P, Theopold C, Hirsch T, Bleiziffer O, Zuhaili B, Fossum M, Hoeller D, Gheerardyn R, Chen M, Visovatti S, Svensson H, Yao F, Eriksson E. Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia. Wound Repair Regen. 2008 Mar-Apr;16(2):288-93. doi: 10.1111/j.1524-475X.2008.00367.x
  35. Fang RC, Kryger ZB, Buck DW, De la Garza M, Galiano RD, Mustoe TA. Limitations of the db/db mouse in translational wound healing research: is the NONcNZO10 polygenic mouse model superior? Wound Repair Regen. 2010 Nov-Dec;18(6):605-13. doi: 10.1111/j.1524-475X.2010.00634.x
  36. Takikawa M, Nakamura S, Nambu M, Sasaki K, Yanagibayashi S, Azuma R, Yamamoto N, Kiyosawa T. New model of radiation-induced skin ulcer in rats. J Plast Surg Hand Surg. 2011 Dec;45(6):258-62. doi: 10.3109/2000656X.2011.633401
  37. Fujita K, Nishimoto S, Fujiwara T, Sotsuka Y, Tonooka M, Kawai K, Kakibuchi M. A new rabbit model of impaired wound healing in an X-ray-irradiated field. PLoS One. 2017 Sep 8;12(9):e0184534. doi: 10.1371/journal.pone.0184534
  38. Bernatchez SF, Parks PJ, Grussing DM, Matalas SL, Nelson GS. Histological characterization of a delayed wound healing model in pig. Wound Repair Regen. 1998 May-Jun;6(3):223-33. doi: 10.1046/j.1524-475x.1998.60308.x
  39. Seaton M, Hocking A, Gibran NS. Porcine models of cutaneous wound healing. ILAR J. 2015;56(1):127-38. doi: 10.1093/ilar/ilv016
  40. Dai T, Kharkwal GB, Tanaka M, Huang YY, Bil de Arce VJ, Hamblin MR. Animal models of external traumatic wound infections. Virulence. 2011 Jul-Aug;2(4):296-15. doi: 10.4161/viru.2.4.16840
  41. Giniuk VA. Metodika modelirovaniia ostrogo mestnogo gnoino-vospalitelnogo protsessa u laboratornykh zhivotnykh i provedeniia eksperimenta po lecheniiu poluchennykh gnoinykh ran s pomoshchiu fotoreguliatornoi i fotodinamicheskoi terapii. Med Zhurn. 2009;(1):44-46. (In Russ.)
  42. Conboy MJ, Conboy IM, Rando TA. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 2013 Jun;12(3):525-30. doi: 10.1111/acel.12065
  43. Kamran P, Sereti KI, Zhao P, Ali SR, Weissman IL, Ardehali R. Parabiosis in mice: a detailed protocol. J Vis Exp. 2013 Oct 6;(80). doi: 10.3791/50556
  44. Mekonnen A, Sidamo T, Asres K, Engidawork E. In vivo wound healing activity and phytochemical screening of the crude extract and various fractions of Kalanchoe petitiana A. Rich (Crassulaceae) leaves in mice. J Ethnopharmacol. 2013 Jan 30;145(2):638-46. doi: 10.1016/j.jep.2012.12.002
  45. Mukherjee H, Ojha D, Bharitkar YP, Ghosh S, Mondal S, Kaity S, Dutta S, Samanta A, Chatterjee TK, Chakrabarti S, Mondal NB, Chattopadhyay D. Evaluation of the wound healing activity of Shorea robusta, an Indian ethnomedicine, and its isolated constituent(s) in topical formulation. J Ethnopharmacol. 2013 Aug 26;149(1):335-43. doi: 10.1016/j.jep.2013.06.045
  46. Kumar V, Khan A, Nagarajan K. Animal models for the evaluation of wound healing activity. Int Bull Drug Res. 2013;3(5):93-107.
  47. Fukai T, Takeda A, Uchinuma E. Wound healing in denervated rat skin. Wound Repair Regen. 2005 Mar-Apr;13(2):175-80. doi: 10.1111/j.1067-1927.2005.130208.x
  48. Yagmur C, Guneren E, Kefeli M, Ogawa R. The effect of surgical denervation on prevention of excessive dermal scarring: a study on rabbit ear hypertrophic scar model. J Plast Reconstr Aesthet Surg. 2011 Oct;64(10):1359-65. doi: 10.1016/j.bjps.2011.04.028
  49. Shanmugam VK, Tassi E, Schmidt MO, McNish S, Baker S, Attinger C, Wang H, Shara N, Wellstein A. Utility of a humanmouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing. Int Wound J. 2015 Dec;12(6):699-705. doi: 10.1111/iwj.12205
  50. Demarchez M, Sengel P, Prunieras M. Wound healing of human skin transplanted onto the nude mouse. I. An immunohistological study of the reepithelialization process. Dev Biol. 1986 Jan;113(1):90-96. doi: 10.1016/0012-1606(86)90110-7
  51. Otulakowski G, Zhou L, Fung-Leung WP, Gendimenico GJ, Samuel SE, Lau CY. Use of a human skin-grafted nude mouse model for the evaluation of topical retinoic acid treatment. J Invest Dermatol. 1994 Apr;102(4):515-18. doi: 10.1111/1523-1747.ep12373180
  52. Lee KO, Kim SN, Kim YC. Anti-wrinkle effects of water extracts of teas in hairless mouse. Toxicol Res. 2014 Dec;30(4):283-89. doi: 10.5487/TR.2014.30.4.283
  53. Simoes D, Miguel SP, Ribeiro MP, Coutinho P, Mendonça AG, Correia IJ. Recent advances on antimicrobial wound dressing: A review. Eur J Pharm Biopharm. 2018 Jun;127:130-41. doi: 10.1016/j.ejpb.2018.02.022
  54. Gaspar-Pintiliescu A, Stanciuc AM, Craciunescu O. Natural composite dressings based on collagen, gelatin and plant bioactive compounds for wound healing: A review. Int J Biol Macromol. 2019 Oct 1;138:854-65. doi: 10.1016/j.ijbiomac.2019.07.155
Address for correspondence:
230009, Belarus,
Grodno, Gorkii Str., 80,
Grodno State Medical University,
the 2nd Surgery Department,
tel.: +375 297 868643,
Dovnar Ruslan I.
Information about the authors:
Dovnar Ruslan I., PhD, Associate Professor of the 2nd Surgery Department Grodno State Medical University, Grodno, Republic of Belarus.
Contacts | ©Vitebsk State Medical University, 2007-2023