A comparative study of the established methods and evaluation of rat trauma models

Abstract

Background: Scientific animal models are indispensable for studying trauma repair. This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers, locations, and trauma attachment tension unloaders and rat age.

Methods: A four-trauma self-upper, lower, left and right control model; a two-trauma self-trauma bare and ring control model; and a young and old rat trauma model were created to evaluate the condition of these traumas.

Results: In the four-trauma self-control model, the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma, whereas there was no significant difference between the left and right trauma. The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side. The healing speed of the old rats was slower, and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats.

Conclusion: The double trauma with a ring is a more scientific and reasonable experimental model. There is a significant difference between young and old rats in the wound healing process. Therefore, the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.

Keywords

age of the rats / healing speed / modeling / rat trauma / skin tension unloader

References

[1] Kalay Z, Cevher SC. Oxidant and antioxidant events during epidermal growth factor therapy to cutaneous wound healing in rats. Int Wound J. 2012; 9(4): 362-371.

[2] Kalin M, Kuru S, Kismet K, et al. The effectiveness of porcine dermal collagen (Permacol((R))) on wound healing in the rat model. Indian J Surg. 2015; 77(Suppl 2): 407-411.

[3] Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR. Topical application of Aloe vera accelerated wound healing, modeling, and remodeling: an experimental study. Ann Plast Surg. 2016; 77(1): 37-46.

[4] Wang Y, Hu Y, Ma B, et al. Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis. J Int Med Res. 2018; 46(6): 2398-2409.

[5] Ozler M, Simsek K, Ozkan C, et al. Comparison of the effect of topical and systemic melatonin administration on delayed wound healing in rats that underwent pinealectomy. Scand J Clin Lab Invest. 2010; 70(6): 447-452.

[6] Park JH, Choi SH, Park SJ, et al. Promoting wound healing using low molecular weight fucoidan in a full-thickness dermal excision rat model. Mar Drugs. 2017; 15(4): 112.

[7] Jalali S, Fereidoni M, Shahri NM, Lari R. Effect of swim bladder matrix treated with hyaluronic acid on wound healing: an animal model evaluation. J Wound Care. 2019; 28(4): 206-213.

[8] Kouketsu A, Shimizu Y, Nogami S, et al. Wound healing effect of autologous fibrin glue and polyglycolic acid sheets in a rat back skin defect model. Transfus Apher Sci. 2021; 60(4): 103144.

[9] Yang JD, Choi DS, Cho YK, et al. Effect of amniotic fluid stem cells and amniotic fluid cells on the wound healing process in a white rat model. Arch Plast Surg. 2013; 40(5): 496-504.

[10] Prestes MA, Ribas CA, Ribas Filho JM, et al. Wound healing using ionic silver dressing and nanocrystalline silver dressing in rats. Acta Cir Bras. 2012; 27(11): 761-767.

[11] Clayton ZE, Tan RP, Miravet MM, et al. Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model. Biosci Rep. 2018; 38(4): BSR20180563.

[12] Hu W, Zhu S, Fanai ML, Wang J, Cai J, Feng J. 3D co-culture model of endothelial colony-forming cells (ECFCs) reverses late passage adipose-derived stem cell senescence for wound healing. Stem Cell Res Ther. 2020; 11(1): 355.

[13] Kim YW, Baek SR, Lee ES, et al. Wound healing effects of rose placenta in a mouse model of full-thickness wounds. Arch Plast Surg. 2015; 42(6): 686-694.

[14] Amini A, Soleimani H, Abdollhifar MA, et al. Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats. J Cell Biochem. 2019; 120(10): 17994-18004.

[15] Amini A, Soleimani H, Rezaei F, Ghoreishi SK, Chien S, Bayat M. The combined effect of photobiomodulation and curcumin on acute skin wound healing in rats. J Lasers Med Sci. 2021; 12: e9.

[16] Bagheri M, Amini A, Abdollahifar MA, et al. Effects of photobiomodulation on degranulation and number of mast cells and wound strength in skin wound healing of streptozotocin-induced diabetic rats. Photomed Laser Surg. 2018; 36(8): 415-423.

[17] Elbialy ZI, Assar DH, Abdelnaby A, et al. Healing potential of Spirulina platensis for skin wounds by modulating bFGF, VEGF, TGF-ss1 and alpha-SMA genes expression targeting angiogenesis and scar tissue formation in the rat model. Biomed Pharmacother. 2021; 137: 111349.

[18] Elbialy ZI, Atiba A, Abdelnaby A, et al. Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and alpha-SMA genes expression. BMC Vet Res. 2020; 16(1): 352.

[19] Gil ES, Panilaitis B, Bellas E, Kaplan DL. Functionalized silk biomaterials for wound healing. Adv Healthc Mater. 2013; 2(1): 206-217.

[20] Golkar N, Ashoori Y, Heidari R, et al. A novel effective formulation of bioactive compounds for Wound healing: preparation, in vivo characterization, and comparison of various postbiotics cold creams in a rat model. Evid Based Complement Alternat Med. 2021; 2021: 8577116.

[21] Li H, Fu X, Zhang L, Huang Q, Wu Z, Sun T. Research of PDGF-BB gel on the wound healing of diabetic rats and its pharmacodynamics. J Surg Res. 2008; 145(1): 41-48.

[22] Zhu FB, Fang XJ, Liu DW, et al. Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus. Neural Regen Res. 2016; 11(3): 493-501.

[23] Aoki K, Ida Y, Fukushima N, Matsumura H. Topical application of oxygen nano-bubble water enhances the healing process of ischaemic skin wound healing in an animal model. Int Wound J. 2022; 19: 1843-1852.

[24] Galiano RD, Michaels J, Dobryansky M, Levine JP, Gurtner GC. Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen. 2004; 12(4): 485-492.

[25] Jin X, Shang Y, Zou Y, et al. Injectable hypoxia-induced conductive hydrogel to promote diabetic wound healing. ACS Appl Mater Interfaces. 2020; 12(51): 56681-56691.

[26] Lee JW, Song KY. Evaluation of a polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam) in a rat wound model. Ann Surg Treat Res. 2018; 94(1): 1-7.

[27] Wang X, Ge J, Tredget EE, Wu Y. The mouse excisional wound splinting model, including applications for stem cell transplantation. Nat Protoc. 2013; 8(2): 302-309.

[28] Atiba A, Nishimura M, Kakinuma S, et al. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-beta and fibroblast growth factor production. Am J Surg. 2011; 201(6): 809-818.

[29] Roh DH, Kang SY, Kim JY, et al. Wound healing effect of silk fibroin/alginate-blended sponge in full thickness skin defect of rat. J Mater Sci Mater Med. 2006; 17(6): 547-552.

[30] Dos Santos Gramma LS, Marques FM, Vittorazzi C, et al. Struthanthus vulgaris ointment prevents an over expression of inflammatory response and accelerates the cutaneous wound healing. J Ethnopharmacol. 2016; 190: 319-327.

[31] Jourdan MM, Lopez A, Olasz EB, et al. Laminin 332 deposition is diminished in irradiated skin in an animal model of combined radiation and wound skin injury. Radiat Res. 2011; 176(5): 636-648.

[32] Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008; 453(7193): 314-321.

[33] Zhang S, Nabi O, Jiang X. New strategy of modulating incision tension: a wound tension offloading device applied before surgery. Dermatol Ther. 2021; 34(2): e14797.

[34] Burgess LP, Morin GV, Rand M, Vossoughi J, Hollinger JO. Wound healing. Relationship of wound closing tension to scar width in rats. Arch Otolaryngol Head Neck Surg. 1990; 116(7): 798-802.

[35] Dorsett-Martin WA. Rat models of skin wound healing: a review. Wound Repair Regen. 2004; 12(6): 591-599.

[36] Duscher D, Maan ZN, Wong VW, et al. Mechanotransduction and fibrosis. J Biomech. 2014; 47(9): 1997-2005.

[37] Desmouliere A, Redard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol. 1995; 146(1): 56-66.

[38] Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. Gerontology. 2013; 59(2): 159-164.

[39] Broughton G, Janis JE, Attinger CE. The basic science of wound healing. Plast Reconstr Surg. 2006; 117(7 Suppl): 12S-34S.

[40] Ma Q, Fan Y, Luo Z, Cui Y, Kang H. Quantitative analysis of collagen and capillaries of 3.8-μm laser-induced cutaneous thermal injury and wound healing. Lasers Med Sci. 2021; 36(7): 1469-1477.

[41] Ballas CB, Davidson JM. Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations. Wound Repair Regen. 2001; 9(3): 223-237.

[42] Velarde MC, Demaria M, Melov S, Campisi J. Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells. Proc Natl Acad Sci USA. 2015; 112(33): 10407-10412.

[43] Andreollo NA, Santos EF, Araujo MR, Lopes LR. Rat's age versus human's age: what is the relationship? Arq Bras Cir Dig. 2012; 25(1): 49-51.

[44] Quinn R. Comparing rat's to human's age: how old is my rat in people years? Nutrition. 2005; 21(6): 775-777.

[45] Rivers JR, Ashton JC. Age matching animal models to humans—theoretical considerations. Curr Drug Discov Technol. 2013; 10(3): 177-181.

[46] Sengupta P. The laboratory rat: relating its age with human's. Int J Prev Med. 2013; 4(6): 624-630.

RIGHTS & PERMISSIONS

2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.