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.

As acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-beta(1). The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-beta(1), with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice.

Here we aim to describe each factor that leads to skin aging and describe their mechanisms. A PubMed database searches (from January 2004 to March 2014) using aging and skin as searched terms. There are substantial evidences showing that aging is associated with damage from free radicals represented by various reactive oxygen species (ROS). Mitochondria are producers and also targets of oxidative stress. The cycle of mitochondrial dysfunction can trigger the aging process. In the cellular senescence and telomeres theory, the diploid cells exhibit a limited proliferation potential. After a finite number of divisions, they enter a state of senescence with a stop replication in cell proliferation. It is suggested that aging is associated mainly with hyper-regulation of apoptosis. Obesity presumably accelerates the process of aging, which is aggravated by smoking. And the influence of the environment, called solar UV irradiation is of considerable importance to skin aging. There are several mechanisms that trigger the natural aging process and contribute to age-related changes, including oxidative stress theory of free radicals, the mitochondrial dysfunction, telomere shortening, UV radiation and other mechanisms that taken together or alone may or not accelerate the change in skin.

Transforming growth factor beta 1 (TGF-beta1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. In this study, we overexpressed TGF-beta1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta1 secretion was measured, as were the effects of TGF-beta1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted approximately 20 times the TGF-beta1 released by control cells, but only cells expressing mutant TGF-beta1 secreted it in the active form. Fibroblasts expressing the active TGF-beta1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta1 formed "keloid-like" nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta1 and prolong cell persistence.

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.