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Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune-competent murine HSc model. A third-degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4',6-diamidino-2-phenylindole. Collagen maturation was assessed with Picro-sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ∼45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild-type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT-PCR showed up-regulation of transforming growth factor beta, alpha smooth muscle actin, and rho-associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues., (© 2014 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of Wound Healing Society.)

Introduction: Patients with postgastric bypass and diet-induced weight loss present to the plastic surgeon for various body contouring procedures. Gross differences in skin dermal elasticity may exist between these populations; however, studies evaluating histologic differences are lacking. This prospective study aims to evaluate histomorphologic differences in morbidly obese patients following surgical versus diet-induced (nonsurgical) weight loss. Further, we aim to elicit if postoperative complications are correlated with the mechanism of weight loss and potential histomorphologic differences., Methods: Defined infraumbilical skin specimens were collected during abdominal contouring procedures following weight loss achieved through surgical or nonsurgical means. Specimens were stained for elastic fiber content and morphology, collagen deposition, and inflammation. All sections underwent evaluation for quality and quantity of elastic fibers, collagen architecture, and presence of inflammation in the context of age-matched controls. Histomorphological results were compared between the 2 groups and subanalyzed according to clinical variables and postbody contouring wound complications., Results: Between July 2008 and December 2010, 30 consecutive patients with significant weight loss (17 surgical, 13 nonsurgical) underwent a panniculectomy (n = 15), abdominoplasty (n = 13), and lower body lift (n = 2), with an average age of 48.3 ± 11.10 years and a body mass index of 39.23 ± 13.65 kg/m. Demographic and clinical variables were not statistically significant between the 2 groups. Blinded histologic evaluation revealed a trend toward normal elastic fiber appearance (P = 0.255), increased wound complications (P = 0.546), and mild inflammation (P = 0.462) in the surgical group. Analysis of dermal histomorphology correlating with wound complications was not statistically significant at follow-up (4.76 ± 5.55 months). Interestingly, there was a persistent inflammatory component in both groups when compared with age-matched controls., Conclusions: Although the differences in histomorphology between the surgical and nonsurgical weight loss groups did not reach statistical significance, the results demonstrated an existence of weight loss-induced histomorphological skin changes that may impact future studies. The study did not demonstrate a relationship between dermal histomorphology and postoperative wound complications, suggesting that aberrant healing in body contouring procedures involves a multifactorial process.

Background: Dermal scarring and scar contracture result in restriction of movement. There are no effective drugs to prevent scarring. RhoA and Rho-associated kinase have emerged as regulators of fibrosis and contracture. Fasudil, a Rho-associated kinase inhibitor, has been demonstrated to have antifibrotic effects in models of liver, renal, and cardiac fibrosis. The role of fasudil in preventing dermal scarring and contractures has not been studied. The authors used a rat model of dermal wound healing to assess the effects of fasudil with regard to the prevention of scarring., Methods: Human scar tissue and surrounding normal skin were immunostained for RhoA and Rho-associated kinase. Full-thickness wounds were created on Wistar-Han rats, and fasudil (30 mg/kg/day) or saline was continuously delivered subcutaneously. Wound contraction was measured by gravitational planimetry. After 21 days, tissue was harvested for Masson's trichrome, hematoxylin and eosin, Ki-67, and CD31 staining. Fibroblast-populated collagen lattices were used to assess the mechanistic effects of fasudil on contractility. Myofibroblast formation was assessed in the presence of fasudil., Results: Human scar tissue in the remodeling phase of repair showed increased expression of RhoA and Rho-associated kinase in scar tissue compared with surrounding normal tissue. Fasudil inhibited wound contraction as compared with controls. Hematoxylin and eosin and Masson's trichrome were similar between groups. Fasudil did not alter angiogenesis or proliferation. Fasudil inhibited fibroblast contractility and myofibroblast formation in vitro., Conclusions: There is growing evidence that the RhoA/Rho-associated kinase pathway plays an important role in wound healing and scar contracture. The authors present data showing that inhibition of Rho-associated kinase hinders fibroblast contractility and may be beneficial in preventing scar contracture.

There is a belief among dermatopathologists that benign melanocytic nevi (BMN) may display atypical histologic characteristics when traumatized. However, to our knowledge, a systematic study of nonsurgically traumatized melanocytic nevi (TMN) has not been published. We studied a series of 92 TMN. Cases were analyzed for histologic evidence of architectural and cytologic criteria associated with atypia. Of the patients, 54 were female and 37 were male. The mean age was 38 years old (range 8-74 years old). Nevi were present, in order of frequency, on the extremities, trunk, and head/neck, but there were no acral sites. Histologic findings of trauma were as follows: parakeratosis (92%), dermal telangiectasias (61%), ulceration (51%), dermal inflammation (49%), melanin within stratum corneum (24%), and dermal fibrosis (25%). Pagetoid spread of melanocytes was limited to the site of trauma in 20% of cases and was identified away from areas of trauma in 8% of cases. Melanocytic atypia was seen in three cases. Dermal mitoses were rare (one mitotic figure in three cases). Pagetoid spread under a traumatized epidermis was relatively frequent and, in isolation, is compatible with a benign TMN. Any traumatized melanocytic lesion that displays cytologic atypia, pagetoid spread outside of the area of the traumatized epidermis, or dermal mitoses should be treated with caution because these findings were rarely seen in TMN.