Establishment of a long-term hypertrophic scar model by injection of anhydrous alcohol: A rabbit model.

The processes of hypertrophic scar formation are extremely complex, and current animal models have limitations in terms of the complete characterization of lesions. An ideal animal model is indispensable for exploring the complex progression of scar formation to elucidate its pathophysiology and to perform therapeutic testing. This study aimed to establish a long-term, consistent and easily testable animal model by injecting anhydrous alcohol into the dorsal trunk dermis of rabbits. The rabbits were injected with different amounts of anhydrous alcohol. Anhydrous alcohol was infiltrated into the subcutaneous and superficial fascia. The optimal amount of anhydrous alcohol was determined by measuring the area and thickness of the scar. The typical model was established by determining the optimum dosage, and then we analysed the histological characteristics and fibrosis-associated protein expression. The dermal scar was generated by treating with 2 ml/kg anhydrous alcohol and displayed histopathologic features that characterize human hypertrophic scarring, including a parallel collagen fibre orientation, dermal and epidermal thickening, broad collagen deposition and the loss of dermal adnexal structures. The expression of fibrotic pan-markers was also enhanced. Moreover, the scar features and duration were compared between the anhydrous alcohol model and the rabbit ear model. Our results show that injecting anhydrous alcohol in the rabbit model thickened the dermal tissue, stimulated dermal fibroproliferation and resulted in hypertrophic scars with protein and histologic features similar to those seen in humans. Taken together, the findings from this study show that our model could be a feasible and useful tool for further research on the pathogenesis of hypertrophic scars.

The role of Th1/Th2 cell chemokine expression in hypertrophic scar.

The aim of this study was to study the role of Th1/Th2 cell-associated chemokines in the formation of hypertrophic scars in rabbit ears. Twenty-six New Zealand white rabbits were used to establish the hypertrophic scar model of rabbit ear and the normal scar model of rabbit's back. Two rabbits were sacrificed on days 0 and 21, 28, 35, 42, 49, 56, and 63 after operation. The specimens were stained with haematoxylin-eosin (HE). Scar elevation index (SEI) was used to detect the expression of 10 chemokines related to Th1/Th2 cells in both scar formation expressions. Real-time polymerase chain reaction (PCR) results showed that two chemokines (CXCL10, CXCL12) were highly expressed during the formation of normal scar, and there was almost no expression during the formation of hypertrophic scar (*P < 0.05). The chemokines (CCL2, CCL3, CCL4, CCL5, CCL7, CCL13, CX3CL1) were almost non-expressed in the formation of normal scars but were expressed for a long time in the formation of hypertrophic scars. The four chemokines, CCL2, CCL4, CCL5, and CX3CL1, maintained a long-term high expression level during the formation of hypertrophic scars (P < 0.01). There were also three chemokines (CCL14, CCL19, CCL21) that were almost undetectable in normal scarring, but there was transiently low-level expression (P < 0.05) only during the peak proliferative phase in proliferative scarring. Th1/Th2 cell-associated chemokines are different in the type, quantity and expression, and maintenance time of rabbit ear hypertrophic scars.

MicroRNA-130a has pro-fibroproliferative potential in hypertrophic scar by targeting CYLD.

Hypertrophic scars are dermal fibrosis diseases that protrude from the surface of the skin and irregularly extend to the periphery, seriously affecting the appearance and limb function of the patient. In this study, we found that microRNA-130a (miR-130a) was increased in hypertrophic scar tissues and derived primary fibroblasts, accompanied by up-regulation of collagen1/3 and α-SMA. Inhibition of miR-130a in hypertrophic scars fibroblasts suppressed the expression of collagen1/3 and α-SMA as well as the cell proliferation. Bioinformatics analysis combined with luciferase reporter gene assay results indicated that CYLD was a target gene of miR-130a, and the miR-130a mimic could reduce the level of CYLD. In contrast to miR-130a, the expression of CYLD was downregulated in hypertrophic scars and their derived fibroblasts. Overexpressing CYLD inhibited the expression of collagen 1/3 and α-SMA, slowed cell proliferation, and inhibited Akt activity. As expected, further study showed that the overexpression of CYLD could prevent the pro-fibroproliferative effects of miR-130a. Consistent with the in vitro results, the inhibitor of miR-130a effectively ameliorated excessive collagen deposition in bleomycin-induced skin fibrosis mouse model. Taken together, our results indicate that miR-130a promotes collagen secretion, myofibroblast transformation and cell proliferation by targeting CYLD and enhancing Akt activity. Therefore, the miR-130a/CYLD/Akt pathway may serve as a novel entry point for future skin fibrosis research.

Observational retrospective study evaluating the effects of oral isotretinoin in keloids and hypertrophic scars.

BACKGROUND: Acne vulgaris is a chronic inflammatory disease characterized by non-inflammatory and inflammatory lesions that can cause scarring. Oral isotretinoin is the current recommended treatment for moderate and severe cases; however, there are reports of possible influences on the healing process of the skin, leading to an increase in the risk for hypertrophic scars and keloids. This hypothesis, although unproven, represents a contraindication to the treatment of acne scars during the 6-12 months after the cessation of isotretinoin. OBJECTIVES: The aim of this study was to investigate the prevalences of hypertrophic scars and keloids in acne patients treated with oral isotretinoin. METHODS: Three data collection strategies were used: (i) clinical examination of patients with acne vulgaris, exposed or unexposed to oral isotretinoin, focusing on the occurrence of hypertrophic scars and/or keloids; (ii) telephone interviews of patients using oral isotretinoin to treat acne vulgaris on the occurrence or worsening of keloids; and (iii) clinical examination of patients with previous use of oral isotretinoin followed at a specific keloid treatment clinic. RESULTS: The resulting data showed no differences in wound healing. CONCLUSIONS: These findings may indicate that the occurrence of hypertrophic scars or keloids in patients using oral isotretinoin is an undesirable event arising from an individual response and may be related to inflammatory acne evolution.

Comparative Study of the Use of Trichloroacetic Acid and Phenolic Acid in the Treatment of Atrophic-Type Acne Scars.

BACKGROUND: Many therapies involving varying degrees of complexity have been used to treat acne scars, but none is considered the gold standard treatment. OBJECTIVE: A comparative evaluation of 88% phenol and 90% trichloroacetic acid (TCA) applied using the chemical reconstruction of skin scars (CROSS) technique. MATERIALS AND METHODS: A nonrandomized, single-blinded self-controlled clinical trial was conducted among patients with ice pick-type and boxcar-type atrophic acne scars. Using 88% phenol on the left hemiface and 90% TCA on the right hemiface was adopted as the standard practice of the CROSS technique. The dermatological quality of life index (DLQI) questionnaire, acne scar grading scale Échelle d´Evaluation Clinique des Cicatrices d'Acne (ECCA), and evaluation of improvement were performed pretreatment and post-treatment. RESULTS: Regarding ECCA, significant differences were found in pretreatment and post-treatment (p < .001). Regarding tolerance to pain, it was found that the discomfort felt with 90% TCA was significantly less than that felt with 88% phenol (p = .020). Regarding the quality of life measured with the DLQI, the results showed that the mean score in post-treatment assessment was significantly lower than that in the pretreatment assessment (p < .05). Hypochromia and enlargement scar were only seen after the use of 90% TCA. CONCLUSION: This study confirmed the efficacy of both TCA and phenol for treating such scars, with less severe complications from the use of phenol.

Depigmentation and hypertrophic scars after application of a fluid lactic acid tattoo eraser.

BACKGROUND: Tattoo removal is often requested by patients. The gold standard is laser tattoo removal that can be time- and cost-intensive. Therefore, safe alternatives without lasers, pain, and scars would be desirable. OBJECTIVE: We wanted to address safety of chemical tattoo erasers. METHODS: We report a case of depigmentation and hypertrophic scars after use of a chemical tattoo eraser and searched the literature. RESULTS: Chemical tattoo erasers are not only used by physicians, but also nonmedical professionals such as beauticians, tattoo artists, and others. The case report we observed and other cases from the literature suggest that lactic acid based tattoo erasers are risky. Available safety data are unsufficient to recommend such procedure as an alternative to current laser therapy. CONCLUSIONS: Chemical tattoo erasers based on lactic acid may be capable to remove tattoo ink but the procedure bears safety risks of permanent adverse effects. For the safety of patients, better regulations for tattoo erasers need to be implemented. Patients need to be informed about adverse effects by such procedures.

A novel murine model of hypertrophic scarring using subcutaneous infusion of bleomycin.

BACKGROUND: The development of new therapies for hypertrophic scarring has been hampered by the lack of an appropriate animal model. The authors' objective was to establish a reproducible murine model of hypertrophic scarring by infusing bleomycin over a prolonged period to stimulate dermal fibroproliferation. METHODS: Osmotic pumps filled with 90 µl of 2.8 mg/ml bleomycin or a control solution (phosphate-buffered saline) were inserted subcutaneously under the dorsal skin of BALB/c mice. The pumps delivered their content at a constant rate of 0.11 µl/hour for 28 days before mice were euthanized or kept alive for a further 28 days and euthanized at day 56. The resulting lesions were analyzed using histological and immunohistochemical techniques. RESULTS: The lesions displayed histopathological features of hypertrophic scar similar to those observed in humans and had increased cellularity, abnormal collagen I-collagen III ratios, elevated levels of the proscarring cytokine transforming growth factor ß1, and increased numbers of myofibroblasts. The 28-day model displayed features analogous to those of a developing human hypertrophic scar, while the 56-day model was analogous to a mature hypertrophic scar. CONCLUSIONS: The bleomycin infusion model stimulates dermal fibroproliferation, creating reproducible murine scars that are comparable to human hypertrophic scars in terms of histological features, collagen content and organization, cellularity, the presence of myofibroblasts, and expression of transforming growth factor ß1. The bleomycin model represents a promising technique for studying scar formation and testing new antiscarring therapies.

Mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy.

The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year-old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease.

[The role of cell pathway in apoptosis of fibroblasts from proliferative scar induced by steroid or IFN].

OBJECTIVE: This paper is to investigate the effects of steroid or IFN alpha-2b on apoptosis and cell pathway of fibroblasts from keloids, hypertrophic scars and normal skins and different responses of different fibroblasts. METHODS: 6 samples from keloid, hypertrophic scar and normal skin were collected respectively and fibroblasts from different sources were cultured in vitro. After different fibroblasts were treated with dexamethasone (0.1 mg/ml) or IFN alpha-2b (1000 U/ml), Bax and Bcl-2 protein expressions were detected in situ by immunohistochemical staining; DNA ladders of different fibroblasts were observed by gel electrophoresis; and relative activated (phospho-) ERK1/2 and JNK pathways were detected by method of FACE ELISA. RESULTS: Dexamethasone could induce apoptosis of fibroblasts from keloids, hypertrophic scars and normal skins through activating (phospho-) ERK1/2 and JNK pathways; IFN alpha-2b could not induce apoptosis of fibroblasts from different sources. IFN alpha-2b could inhibit (phospho-) ERK1/2 pathway and could not affect (phospho-) JNK pathways of fibroblasts from keloid and hypertrophic scar. IFN alpha-2b could affect neither (phospho-) ERK1/2 pathway nor (phospho-) JNK pathways of fibroblasts from normal skin. CONCLUSIONS: The responses of different fibroblasts to steroid or IFN alpha-2b were different.

Delayed reepithelialization and scarring deregulation following drug-induced toxic epidermal necrolysis.

A 51-year-old Caucasian woman developed severe drug-induced toxic epidermal necrolysis (TEN) due to allopurinol. The withdrawal of the culprit drug was unfortunately delayed, and dramatic retardation of reepithelialization was observed. At that stage of disease evolution, an inflammatory cell infiltrate was present in the dermis. Coverage of eroded lesions by frozen cultured keratinocyte allografts failed to hasten reepithelialization compared to ungrafted sites. This unusual protracted TEN evolution was followed by the development of extensive hypertrophic and keloid scars. Several biopsies were taken over 6 months. The histologic presentation of the grafted and ungrafted eroded scar tissues looked similar. Both the number and size of the Factor XIIIa-positive dermal dendrocytes, as well as the number of alpha-actin-positive myofibroblasts showed a marked increase between weeks 2 and 12 after grafting. They were reduced after 6 months when the scarring process was stabilized. alpha1 [IV] collagen was never expressed over the eroded scars. Similar to burn patients, delayed reepithelialization might be a risk factor for abnormal scarring in TEN. Cultured keratinocyte allograft apparently offered no improvement in reepithelialization and did not prevent abnormal scarring in this TEN patient.

[A research of endothelial cell-targeted therapy for cure of hypertrophic scar].

OBJECTIVE: To investigate the feasibility of endothelial cell-targeted therapy to cure post-burn hypertrophic scar. METHODS: A hypertrophic scar animal model was made. Intralesional injecting of VEGF monoclonal antibody was performed for three weeks. The changes of scar in volume and morphology were observed. RESULTS: 1. The volume of scar decreased. 2. The number of the capillary, the amount of collagen I and collagen III decreased. 3. Transmission electron microscope examinations demonstrated many dead or apoptotic fibroblasts and endothelial cells. Fibrocytes were seen relatively common. CONCLUSION: VEGF induces the growth and development of hypertrophic scar in that it induces excessive and uncontrollable angiogenesis, which favors excessive collagen synthesis. Endothelial cell-targeted therapy may be a promising method to cure post-burn hypertrophic scar.