Clinical applications of basic research that shows reducing skin tension could prevent and treat abnormal scarring: the importance of fascial/subcutaneous tensile reduction sutures and flap surgery for keloid and hypertrophic scar reconstruction.
ABSTRACT We use evidence-based algorithms to treat abnormal scarring, including keloids and hypertrophic scars (HSs). This involves a multimodal approach that employs traditional methods such as surgical removal, postoperative radiotherapy, corticosteroid injection, laser, and silicone gel sheets. As a result, the rate of abnormal scarring recurrence has decreased dramatically over the past 10 years. However, several problems remain to be solved. First, despite the optimization of a radiotherapy protocol, over 10% of cases who are treated with surgery and postoperative radiotherapy still recur in our facility. Second, the treatment options for cases with huge keloids are very limited. To address these problems, we performed basic research on the mechanisms that drive the formation of keloids and HSs. Extrapolation of these research observations to the clinic has led to the development of two treatment strategies that have reduced the rate of abnormal scar recurrence further and provided a means to remove large scars. Our finite element analysis of the mechanical force distribution around keloids revealed high skin tension at the keloid edges and lower tension in the keloid center. Moreover, when a sophisticated servo-controlled device was used to stretch wounded murine dorsal skin, it was observed that the stretched samples exhibited upregulated epidermal proliferation and angiogenesis, which are also observed in keloids and HSs. Real-time RT-PCR also revealed that growth factors and neuropeptides are more strongly expressed in cyclically stretched skin than in statically stretched skin. These findings support the well-established notion that mechanical forces on the skin strongly influence the cellular behavior that leads to scarring. These observations led us to focus on the importance of reducing skin tension when keloids/HSs are surgically removed to prevent their recurrence. Clinical trials revealed that subcutaneous/fascial tensile reduction sutures, which apply minimal tension on the dermis, are more effective in reducing recurrence than the three-layered sutures used by plastic surgeons. Moreover, we have found that by using skin flaps (e.g., perforator flaps and propeller flaps), which release tension on the wound, in combination with postoperative radiotherapy, huge keloids can be successfully treated.
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ABSTRACT: Background. Clinically, scar related complications are observed to be dissimilar in different regions of the body. Unequal distribution of dermal collagen and elastic fibres in different orientations could be one of the multifocal causes of scar related complications, for which this evaluating study has been taken up. Materials and Method. 300 skin samples collected in horizontal and vertical orientations were studied histomorphometrically. This study involved image analysis of specially stained histological section using tissue-quant software. The outcome result was termed as quantitative fraction. From the result, various ratio values were also calculated for the ratio analysis. Results. The differences in the quantitative fraction of dermal elastic content between 2 directions were statistically significant at joint areas (shoulder joint, wrist, and ankle) (P < 0.001) but for collagen, significant difference was observed at shoulder joint and wrist only. Dermis of the forearm and thigh did not show any differences in their collagen content, but for elastic, thigh did show a significant difference while forearm had no change between 2 directions. Conclusion. Analysis of unequal content of dermal element in two directions under the perspective of wound healing consequences is subjective depending upon the anatomical position and functional status of the areas.
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ABSTRACT: Among raised dermal scar types, keloid (KS) and hypertrophic scars (HS) are considered to present clinical similarities, but there are no known specific biomarkers that allow both scar types to be easily distinguished. Development and progression of raised dermal scars comprises the activation of several molecular pathways and cell defence mechanisms leading to elevated extracellular matrix component synthesis, delayed apoptosis, altered migration and differentiation. Therefore, the aim here was to identify biomarkers that may differentiate between KS and HS compared to normal skin (NS). To achieve this aim, NS (n = 14), KS (n = 14) and HS (n = 14) biopsies were evaluated using histology by H&E staining. Tissue biopsies and primary fibroblasts (passages 0-4) were employed to assess the gene expression levels of 21 biomarkers selected from our previous microarray studies using qRT-PCR. Finally, protein expression was evaluated using In-Cell Western Blotting in primary fibroblasts (p 0-4). Our results demonstrated that out of the 21 biomarkers screened at mRNA and protein levels, α2β1-integrin, Hsp27, PAI-2, MMP-19 and CGRP showed significantly higher expression (p < 0.05) in KS compared to NS and HS. Additionally, these five key biomarkers were found to be significantly higher (p < 0.05) at mRNA level in KS taken from the sternum, a region known to be subjected to high mechanical forces in the body during the performance of daily movements. In conclusion, our findings offer potential molecular targets in raised dermal scars differentiation. Future targeted research may allow provision of diagnostic and prognostic markers in keloid versus hypertrophic scarsArchives for Dermatological Research 10/2014; 307(2). DOI:10.1007/s00403-014-1512-4 · 2.27 Impact Factor
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ABSTRACT: The development of cutaneous pathological scars, namely, hypertrophic scars (HSs) and keloids, involves complex pathways, and the exact mechanisms by which they are initiated, evolved, and regulated remain to be fully elucidated. The generally held concepts that keloids and HSs represent "aberrant wound healing" or that they are "characterized by hyalinized collagen bundles" have done little to promote their accurate clinicopathological classification or to stimulate research into the specific causes of these scars and effective preventative therapies. To overcome this barrier, we review here the most recent findings regarding the pathology and pathogenesis of keloids and HSs. The aberrations of HSs and keloids in terms of the inflammation, proliferation, and remodeling phases of the wound healing process are described. In particular, the significant roles that the extracellular matrix and the epidermal and dermal layers of skin play in scar pathogenesis are examined. Finally, the current hypotheses of pathological scar etiology that should be tested by basic and clinical investigators are detailed. Therapies that have been found to be effective are described, including several that evolved directly from the aforementioned etiology hypotheses. A better understanding of pathological scar etiology and manifestations will improve the clinical and histopathological classification and treatment of these important lesions.07/2013; 1(4):e25. DOI:10.1097/GOX.0b013e31829c4597