Wound healing in hypertrophic scarring and keloid animal models presents significant differences when compared with humans. A brief review is presented about hypertrophic scarring in animal models during the last 5 years. Models were described by animals and scientific artifices to cause hypertrophic scarring. They were divided into 1) heterologous hypertrophic scarring or keloid implants in immunodeficient animals (athymic mice and rats); 2) heterologous hypertrophic scarring or keloid implant in immune privileged site (hamster cheek pouch); 3) hypertrophic scarring or keloid induction via chemically mediated injury (guinea pigs); 4) hypertrophic scarring or keloid induction in anatomic specific site (rabbit ear); and the 5) porcine model. The ideal model would allow to research pathophysiology, histology, and molecular events during time and to test prophylactic and therapeutic treatments for humans. Some of these animals were useful to study specific steps of the scarring process and better understand abnormal wound healing, but none of them have a widespread use. Most recently, the female red Duroc pigs were validated as a new model, demonstrating its similarity to human conditions in different ways. Full-thickness human skin grafts in nude mice also represent improvement in the search of an ideal hypertrophic scarring animal model.
PURPOSE:To revise and systematize scientific knowledge of the experimental model for cutaneous burns in rats. METHODS:A bibliographical review from 2008 up to January 2011 in PubMed, EMBASE and LILACS was undertaken. Were used the keywords: animal models, burns and rats. 221 studies were identified, and 116 were selected. RESULTS:It was found that: 54/86 (62.7%) had third degree burns; 55/73 (75.3%) studied the back; 45/78 (57.6%) used heated water and 27/78 (35.9%) incandescent instruments; 39/78 (50%) studied systemic effects; 22/71 (31%) used ketamine associated with xylazine; 61/64 (95.3%) performed depilation with appropriate equipment; 36/72 (50%) used microscopy; more than 50% did not describe analgesia or antibiotics during the postoperative period; in 42/116 (36.2%) postoperative fluid therapy was performed; and the time interval after the burn, up to the beginning of the results analysis varied from 7s up to four weeks. Legislation issues on burn experiments are discussed. CONCLUSION:The hot water was the main method to induce burns those of third degree on the back, with anesthesia using ketamine and xylazine, after depilation. These were evaluated microscopically, without using analgesia or an antibiotic during the postoperative period. The studies were not very reproducible. CONCLUSÃO: Líquido aquecido foi o principal método para induzir queimadura de terceiro grau no dorso do animal, com anestesia usando quetamina e xilazina, após depilação, avaliados por microscopia, sem uso de analgesia ou antibióticos. Os estudos não são reprodutíveis.Descritores: Modelos Animais. Queimaduras. Pele. Revisão. Ratos.Mitsunaga Jr JK et al.
BackgroundHypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete.Methodology/Principal FindingsWe have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model.Conclusions/Significance1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.
Continuous expansion using an infusion pump was studied in seven patients. Tissue expanders were attached to outpatients under general anesthesia. After a period of 7 days, the skin expansion was initiated with the patient hospitalized. Saline solution (0.9%, 1-3 ml/h) was infused via a gauge needle connected to the expander valve and to the infusion pump. The expansion speed was determined by clinical parameters, such as pain and the expanded tissue viability, until the desired volume was achieved. The total time required for this procedure was 13-18 days. Based on continuous skin expansion, we attempted to test an alternative shorter procedure. This method was well accepted by doctors and patients, and no complications occurred. Although fibrosis was observed, it was not as pronounced as in the outpatients undergoing the conventional expansion treatment. A principal advantage of the continuous expansion method is the increased safety resulting from more effective clinical control and adequate systemic antibiotic therapy. Coupled with on important reduction the expansion time and allowing a faster return of the patients to their activities.
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