Deneysel Yara Modelleri
Özet
Deneysel yara iyileşmesi modelleri, doku onarımı süreçlerini anlamak ve klinik tedavi stratejileri geliştirmek amacıyla in vitro ve in vivo olarak iki grupta uygulanan önemli biyolojik araçlardır. Hücre ve doku kültürleri ile 3D matrikslerin kullanıldığı in vitro modeller, yara iyileşmesindeki hücresel ilişkileri ve tepkileri inceler ancak dış etmenlerin etkisini ölçemedikleri için tam fizyolojik koşulları sağlayamazlar. Klinik durumlara daha çok benzeyen in vivo modellerde ise insan derisine benzerliği nedeniyle domuzlar, bakımı kolay olduğu için sıçanlar ve genetik çalışmalar için fareler tercih edilir. In vivo akut yara modelleri (insizyonel, eksizyonel, ölü boşluk ve termal/kimyasal yanıklar), yara iyileşmesinin fizyolojik gelişimini ve çevresel faktörlerin etkilerini araştırır. Tedavisi zor olan durumları inceleyen kronik yara modelleri ise iskemi oluşturma, damar ligasyonu, tavşan kulağı ülseri, köpeklerde dekübit taklidi, yüksek kalsiyum konsantrasyonu enjeksiyonu ve andriamisin veya örümcek zehri gibi farmakolojik ajanların kullanımıyla elde edilir. Ayrıca güncel araştırmalar; diyabet, obezite ve malnütrisyon gibi metabolik yöntemlerin yanı sıra enfeksiyon, iskemi ve glukokortikosteroid, radyasyon veya T lenfosit eksikliği olan özel hayvanların kullanıldığı immünolojik modeller aracılığıyla yara iyileşmesini bozan etkenleri ve tedavi yanıtlarını taklit ederek güvenilir bilgiler sunmaktadır.
Experimental wound healing models are important biological tools applied in two groups as in vitro and in vivo to understand tissue repair processes and develop clinical treatment strategies. In vitro models using cell and tissue cultures with 3D matrixes examine cellular relationships and responses in wound healing, but they cannot provide full physiological conditions since they cannot measure the effects of external factors. In vivo models, which resemble clinical situations more closely, prefer pigs due to their similarity to human skin, rats for their ease of care, and mice for genetic studies. In vivo acute wound models (incisional, excisional, dead space, and thermal/chemical burns) investigate the physiological development of wound healing and the effects of environmental factors. Chronic wound models studying difficult-to-treat conditions are obtained by inducing ischemia, vessel ligation, rabbit ear ulcers, decubitus mimicking in dogs, high calcium concentration injection, and the use of pharmacological agents such as adriamycin or spider venom. Furthermore, current research provides reliable information by mimicking factors impairing wound healing and treatment responses through metabolic methods like diabetes, obesity, and malnutrition, as well as immunological models utilizing infection, ischemia, glucocorticosteroids, radiation, or special animals with T-lymphocyte deficiency.
Referanslar
Romanelli M, Miteva M, Romanelli P, et al. Use of diagnostics in wound management. Curr Opin Support Palliat Care. 2013;7:106-110. doi: 10.1097/SPC. 0b013e32835dc0fc.
Andrade TA, Iyer A, Das PK et al. The inflammatory stimulus of a natural latex biomembrane improves healing in mice. Braz J Med Biol Res. 2011;44:1036-1047. doi: 10.1590/s0100-879x2011007500116
Leite SN, Andrade TA, Masson-Meyers DS, et al. Phototherapy promotes healing of cutaneous wounds in undernourished rats. An Bras Dermatol. 2014;89:899-904. doi: 10.1590/abd1806-4841.20143356
Leite SN, Leite MN, Caetano GF, et al. Phototherapy improves wound healing in rats subjected to high-fat diet. Lasers Med Sci. 2015;30:1481-1488. doi:10.1007/s10103-015-1745-2
Baktır G. Wound Repair and Experimental Wound Models. Experimed 2019; 9(3): 130-7 doi: 10.1111/iep.12346
Greenhalgh DG. Models of wound healing. J Burn Care Rehabil 2005; 26: 293-305. doi: 10.1097/01.bcr.0000169885.66639.b5.
Bettinger DA, Yager DR, Diegelmann RF, Cohen IK. The effect of TGF-beta on keloid fibroblast proliferation and collagen synthesis. Plast Reconstr Surg 1995;98: 827-33. doi: 10.1097/00006534-199610000-00012
Aydın OE, Tan Ö, Çinal H, Kara M, Çakmak MA. Deneysel Yara Modelleri. Turkiye Klinikleri J Plast Surg-Special Topics 2015; 4: 5-11.
Emanualsson P, Kratz G. Characterization of a new in vitro burn wound model. Burns 1997; 23: 32-6. doi:10.1016/s0305-4179(96)00073-3
Strande LF, Foley ST, Doolin EJ, et al. In vitro bioartifi cial skin culture model of tissue rejection and inflammatory/ immune mechanisms. Transplant Proc 1997;29: 2118-9. doi: 10.1016/s0041-1345(97)00256-x
Nandi S, Brown AC. Characterizing cell migration within three-dimensional in vitro wound environments. J Vis Exp 2017. doi: 10.3791/56099
Dorsett-Martin WA. Rat models of skin wound healing: a review. Wound Repair Regen 2004; 12: 591-9. doi: 10.1111/j.1067-1927.2004.12601.x
Sullivan TP, Eaglstein WH, Davis SC, et al. The pig as a model for human wound healing. Wound Repair Regen 2001; 9: 66-76. doi: 10.1046/j.1524-475x.2001.00066.x
Wong VW, Sorkin M, Glotzbach JP, et al. Surgical approaches to create murine models of human wound healing. J Biomed Biotechnol 2011; doi:10.1155/2011/969618. doi: 10.1155/2011/969618
Experimental Animal Wound Models. Department of Pathology, Vanderbilt University School of Medicine and Research Service, Department of Veterans Affairs Medical Center, Nashville, Tennessee
Ansell DM, Campbell L, Thomason HA, et al. A statistical analysis of murine incisional and excisional acute wound models. Wound Repair Regen. 2014 Mar;22(2):281-7. doi: 10.1111/wrr.12148
Breuing K, Eriksson E, Liu P, et al. Healing of partial thickness porcine skin wounds in a liquid environment. J Surgical Research 1992;52:50-8. doi:10.1016/0022-4804(92)90278-8
Galiano RD, Michaels VJ, Dobryansky M, et al. Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen 2004; 12:485-92.doi: 10.1111/j.1067-1927.2004.12404.x
Diegelmann RF, Lindblad WJ Cohen IK. A subcutaneous implant for wound healing studies in humans. J Surg Res 1986; 40: 229-37. doi: 10.1016/0022-4804(86)90156-3
Kurkinen M, Vaheri A, Roberts PJ, et al. Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Med 1980; 43: 47-51
Greenhalgh DG. Models of wound healing. J Burn Care Rehabil2005; 26: 293-305 doi: 10.1097/01.bcr.0000169885.66639.b5.
Greenhalgh DG, Gamelli RL. Immunomodulators and wound healing. J Trauma 1987; 27: 510-4 doi:10.1097/00005373-198705000-00009
Auerbach LJ, Galvez MG, De Clerck BK, et al. Anovel mouse model for frostbite injury. Wilderness Environ Med 2013; 24: 94-104. doi: 10.1016/j.wem.2012.11.020
Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar. J Burn Care Rehab 1993;14:544-51.doi: 10.1097/00004630-199309000-00009
Stricklin GP, Li L, Nanney LB. Localization of mR-NAs representing interstitial collagenase, 72-kda gelatinase, and TIMP in healing porcine burn wounds. J Invest Dermatol 1994;103:352-8. doi: 10.1111/1523-1747.ep12394926
Elmas O, Cevik M2, Demir T, Ketani MA. Effect of oral tamoxifen on the healing of corrosive oesop hageal burns in an experimental rat model. Interact Cardiovasc Thorac Surg. 2014 Sep;19(3):351-6. doi:10.1093/icvts/ivu185
Constantine BE, Bolton LL. A wound model for is chemic ulcers in the guinea pig. Arch Dermatologic Res 1986;278:429-31 doi: 10.1007/BF00418177
Ahn ST, Mustoe TA. Effects of ischemia on ulcer wound healing: A new model in the rabbit ear. Ann Plast Surg 1990;24:17-23. doi: 10.1097/00000637-199001000-00004
Sank A, Chi M, Shima T, et al. Increased calcium levels alter cellular and molecular events in wound healing. Surgery 1989;106:1141-7; discussion 7-8.
Rudolph R, Suzuki M, Luce JK. Experimental skin necrosis produced by Adriamycin. Cancer Treatment Reports 1979;63:529-37.
DeLozier JB, Reaves L, King LE, et al. Brown recluse spider bites of the upper extremity. South Med J 1988;81:181-4. doi: 10.1097/00007611-198802000-00009
Greenhalgh DG. Wound healing and diabetes melltus. Clin Plastic Surg 2003; 30: 37-45. doi: 10.1016/s0094-1298(02)00066-4
Brown RL, Breeden MP, Greenhalgh DG. PDGF and TGF-alpha act synergistically to improve wound healing in the genetically diabetic mouse. J Surg Res 1994; 56: 562-70. doi: 10.1006/jsre.1994.1090
Tsuboi R, Rifkin DB. Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice. J Exp Med 1990; 172: 245-51 doi: 10.1084/jem.172.1.245
Rerup CC. Drugs producing diabetes through dama ge of insülin secreting cells. Pharmacol Rev 1970; 22:485-518.
Goodson WHd, Hunt TK. Deficient collagen for mation by obese mice in a standard wound model. Am J Surg 1979;138:692-4. doi: 10.1016/0002-9610(79)90350-7
Levenson SM, Demetriou AA. Metabolic factors. In: Cohen IK, Diegelmann RF, Lindblad WJ (eds). Wound Healing: Biochemical and Clinical Aspects. Philadelphia, PA: WB Saunders, 1992:248-73.
Alvarez OM, Gilbreath RL. Thiamine influence on collagen during the granulation of skin wounds. J Surg Res 1982; 32: 24-31. doi: 10.1016/0022-4804(82)90180-9
Levenson SM, Kan-Gruber D, Gruber C, et al. Wound healing accelerated by Staphylococcus aureus. Arch Surg 1983; 118: 310-20. doi: 10.1001/archsurg.1983.01390030042007
Traeger T, Koerner P, Kessler W, et al. Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis. J Vis Exp 2010;46: 2299. doi: 10.3791/2299.
Corral CJ, Siddiqui A, Wu L, et al. Vascular endot helial growth factor is more important than basic fibroblastic growth factor during ischemic wound healing. Arch Surg 1999;134: 200-5. doi: 10.1001/archsurg.134.2.200.
Serin ve Bayramiçli M. Experimental Rat Flap Models 2018; Available from: https://www.intechopen.com/books/issues-in-flapsurgery/experimental-rat-flap-models
Daniel RK, Wheatley DC, Priest DL. Pressure sores and paraplegia: an experimental model. Ann Plast Surg 1985; 15: 41-9. doi: 10.1097/00000637-198507000-00005.
Hyodo A, Reger SI, Negami S, et al. Evaluation of a pressure sore model using monoplegic pigs. Plast Reconstr Surg 1995; 96: 421-8 doi: 10.1097/00006534-199508000-00025.
Laato M, Heino J, Kahari VM, et al. Epidermal growth factor (EGF) prevents methylprednisolone-induced inhibition of wound healing. J Surg Res 1989; 47: 354-9. doi: 10.1016/0022-4804(89)90147-9.
Curtsinger LJ, Pietsch JD, Brown GL, et al. Reversal of Adriamycin-impaired wound healing by trans forming growth factor-beta. Surgery, Gynecology &Obstetrics 1989;168:517-22.
Barbul A, Shawe T, Rotter SM, et al. Wound healing in nude mice: A study on the regulatory role of lymp- hocytes in fibroplasia. Surgery 1989;105:764-9.
Démarchez M, Hartmann DJ, Herbage D, et al. Wound healing of human skin transplanted onto the nude mouse. Develop Biol 1987;121:119-29. doi: 10.1016/0012-1606(87)90145-x.
Leibovitch SJ, Ross R. The role of the macrophage in wound repair: A study with hydrocortisone and anti macrophage serum. Am J Pathol 1975;78:71-100
Lefaix JL, Martin M, Tricaud Y,et al. Muscular fibrosis induced after pig skin irradiation with single doses
