References

Nageswaran S, Vijayakumar R, Sivarasu S. Design of mechanical interface to re-distribute excess pressure to prevent the formation of decubitus ulcers in bed ridden patients. Conf Proc IEEE Eng Med Biol Soc. 2015; 1021-1024 https://doi.org/10.1109/EMBC.2015.7318538

Demarré L, Van Lancker A, Van Hecke A The cost of prevention and treatment of pressure ulcers: A systematic review. Int J Nurs Stud. 2015; 52:(11)1754-1774 https://doi.org/10.1016/j.ijnurstu.2015.06.006

Barateau M, Gautier Y. Mobilising the team and the patient to prevent pressure ulcers. Rev Infirm. 2018; 67:(239)38-39 https://doi.org/10.1016/j.revinf.2018.01.010

Järbrink K, Ni G, Sönnergren H The humanistic and economic burden of chronic wounds: a protocol for a systematic review. Syst Rev. 2017; 6 https://doi.org/10.1186/s13643-016-0400-8

Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther. 2017; 34:(3)599-610 https://doi.org/10.1007/s12325-017-0478-y

de Macedo GMC, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabetol Metab Syndr. 2016; 8:(1) https://doi.org/10.1186/s13098-016-0176-y

Horton WB, Boler PL, Subauste AR. Diabetes mellitus and the skin: recognition and management of cutaneous manifestations. South Med J. 2016; 109:(10)636-646 https://doi.org/10.14423/SMJ.0000000000000541

Emanuelli T, Burgeiro A, Carvalho E. Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers. Arch Dermatol Res. 2016; 308:(10)677-694 https://doi.org/10.1007/s00403-016-1686-z

Jhamb S, Vangaveti VN, Malabu UH. Genetic and molecular basis of diabetic foot ulcers: clinical review. J Tissue Viability. 2016; 25:(4)229-236 https://doi.org/10.1016/j.jtv.2016.06.005

Mauricio D, Jude E, Piaggesi A, Frykberg R. Diabetic foot: current status and future prospects. J Diabetes Res. 2016; 2016 https://doi.org/10.1155/2016/5691305

Trujillo AN, Kesl SL, Sherwood J Demonstration of the rat ischemic skin wound model. J Vis Exp. 2015; 98 https://doi.org/10.3791/52637

Sami DG, Heiba HH, Abdellatif A. Wound healing models: a systematic review of animal and non-animal models. Wound Med. 2019; 24:(1)8-17 https://doi.org/10.1016/j.wndm.2018.12.001

Wong VW, Sorkin M, Glotzbach JP Surgical approaches to create murine models of human wound healing. BioMed Res Int. 2011; 2011 https://doi.org/10.1155/2011/969618

Seaton M, Hocking A, Gibran NS. Porcine models of cutaneous wound healing. ILAR J. 2015; 56:(1)127-138 https://doi.org/10.1093/ilar/ilv016

National institutes of Health. Guide for the care and use of laboratory animals. 2011. https://tinyurl.com/v9dvouc (accessed 7 July 2020)

Silverman J, Suckow MA, Murthy S. The IACUC Handbook, 3rd edn. Boca Raton, FL, US: CRC Press, Taylor & Francis Group; 2014

Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2015; 70:5.47.1-20 https://doi.org/10.1002/0471141755.ph0547s70

Mendes JJ, Leandro CI, Bonaparte DP, Pinto AL. A rat model of diabetic wound infection for the evaluation of topical antimicrobial therapies. Comp Med. 2012; 62:(1)37-48

Takeuchi Y, Ueno K, Mizoguchi T Development of novel mouse model of ulcers induced by implantation of magnets. Sci Rep. 2017; 7 https://doi.org/10.1038/s41598-017-05250-y

Martínez-De Jesús FR. A checklist system to score healing progress of diabetic foot ulcers. Int J Low Extrem Wounds. 2010; 9:(2)74-83 https://doi.org/10.1177/1534734610371594

Strauss MB, Moon H, Busch JA Reliability assessment of an innovative wound score. Wounds. 2016; 28:(6)206-213

Perez D, Bramkamp M, Exe C Modern wound care for the poor: a randomized clinical trial comparing the vacuum system with conventional saline-soaked gauze dressings. Am J Surg. 2010; 199:(1)14-20 https://doi.org/10.1016/j.amjsurg.2008.12.029

Huang Y, Xie T, Cao Y Comparison of two classification systems in predicting the outcome of diabetic foot ulcers: the Wagner grade and the Saint Elian Wound score systems. Wound Repair Regen. 2015; 23:(3)379-385 https://doi.org/10.1111/wrr.12289

Suvarna KS, Layton C, Bancroft JD. Bancroft's theory and practice of histological techniques e-book.: Elsevier Health Sciences; 2018

Gál P, Kilík R, Mokrý M Simple method of open skin wound healing model in corticosteroid-treated and diabetic rats: standardization of semi-quantitative and quantitative histological assessments. Veterinarni Medicina. 2008; 53:652-659 https://doi.org/10.17221/1973-VETMED

Iyun AO, Ademola SA, Olawoye OA Point prevalence of chronic wounds at a tertiary hospital in Nigeria. Wounds. 2016; 28:(2)57-62

Ud-Din S, Bayat A. Non-animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin. Wound Repair Regen. 2017; 25:(2)164-176 https://doi.org/10.1111/wrr.12513

Menke NB, Cain JW, Reynolds A An in silico approach to the analysis of acute wound healing. Wound Repair Regen. 2010; 18:(1)105-113 https://doi.org/10.1111/j.1524-475X.2009.00549.x

Bai Y, Zang X, Ma J, Xu G. Anti-diabetic effect of Portulaca oleracea L. polysaccharide and its mechanism in diabetic rats. Int J Mol Sci. 2016; 17:(8) https://doi.org/10.3390/ijms17081201

Spanheimer RG, Umpierrez GE, Stumpf V. Decreased collagen production in diabetic rats. Diabetes. 1988; 37:(4)371-376 https://doi.org/10.2337/diab.37.4.371

Stadler I, Zhang R-Y, Oskoui P Development of a simple, noninvasive, clinically relevant model of pressure ulcers in the mouse. J Invest Surg. 2004; 17:(4)221-227 https://doi.org/10.1080/08941930490472046

Reid RR, Sull AC, Mogford JE A novel murine model of cyclical cutaneous ischemia-reperfusion injury. J Surg Res. 2004; 116:(1)172-180 https://doi.org/10.1016/s0022-4804(03)00227-0

Wassermann E, van Griensven M, Gstaltner K A chronic pressure ulcer model in the nude mouse. Wound Repair Regen. 2009; 17:(4)480-4 https://doi.org/10.1111/j.1524-475X.2009.00502.x

Maldonado AA, Cristóbal L, Martín-López J A novel model of human skin pressure ulcers in mice. PLoS One. 2014; 9:(10) https://doi.org/10.1371/journal.pone.0109003

European Pressure Ulcer Advisory Panel, National Pressure Injury Advisory Panel and Pan Pacific Pressure Injury Alliance. Prevention and treatment of pressure ulcers/injuries: quick reference guide. 2019. https://www.epuap.org/download/11182

Pradhan L, Nabzdyk C, Andersen ND Inflammation and neuropeptides: the connection in diabetic wound healing. Expert Rev Mol Med. 2009; 11 https://doi.org/10.1017/S1462399409000945

Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. 2006; 23:(6)594-608 https://doi.org/10.1111/j.1464-5491.2006.01773.x

Larouche J, Sheoran S, Maruyama K, Martino MM. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv Wound Care. 2018; 7:(7)209-231 https://doi.org/10.1089/wound.2017.0761

Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther. 2014; 31:(8)817-836 https://doi.org/10.1007/s12325-014-0140-x

Histological and clinical evaluation of wound healing in pressure ulcers: a novel animal model

01 June 2021

Abstract

Objective:

Pressure ulcers (PUs) are a major healthcare problem, commonly associated with older people, patients who are bedbound and patients with diabetes. The impact of PUs can decrease patients' quality of life, and lead to high morbidity and mortality rates. In this study, we aimed to describe a novel PU model that simulates pressure ulcers in humans to provide a research tool for new drug testing.

Method:

Diabetes was induced using streptozocin in 75 adult Sprague Dawley rats. To create the PU, skin was sandwiched between two magnets, one of them implanted below the panniculus carnosus muscle and the other above the skin. The model was tested on nondiabetic rats and diabetic rats, each with pressure ulcers, compared to nondiabetic rats with excisional wounds.

Results:

Results showed that the PU model in diabetic (p-value<0.000001) and non-diabetic rats (p-value<0.05) exhibited significantly delayed healing (no healing over 21 days) compared with the excisional wound that was completely healed by day 21.

Conclusion:

Diabetic rats showed significant changes in intact skin compared with non-diabetic rats, as well as a significant delay in the healing process compared with the non-diabetic group. By effectively impairing the skin contraction otherwise seen in the rats, and thereby delaying healing and making it similar to that seen in hard-to-heal PUs in humans, this model provides an effective tool for wound healing research.

Pressure ulcers (PUs) are major complications of chronic diseases such as diabetes, venous and arterial insufficiency, and dysfunction of the microvascular system.1,2,3 Over the past few decades, the prevalence of hard-to-heal ulcers has dramatically increased, creating a huge financial burden on healthcare systems.4,5 As the prevalence of diabetes increases, the incidence of diabetic complications is expected to increase.6,7,8,9,10

The main causative factors involved in the pathogenesis of PUs are mechanical pressure, shear and friction forces, and moisture.11 The normal healing process of the skin is characterised by the following phases: coagulation, acute inflammation, proliferation and remodelling.11 In hard-to-heal ulcers, the healing process is impaired due to tissue ischaemia, poor lymphatic drainage and infection, which eventually impairs granulation tissue formation and prolongs wound repair. Here, we focus mainly on hard-to-heal PUs in uncontrolled diabetes.

Register now to continue reading

Thank you for visiting Journal of Wound Care's World Union of Wound Healing Supplement and reading some of our peer-reviewed resources for healthcare professionals. To read more, please register today.