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Background: The prominent inflammatory cell identified in excessive scarring is the mast cell. Hypertrophic scar exhibits myofibroblasts derived from the transformation of fibroblasts, increased collagen synthesis, and stationary nonmigratory resident cells. The co-culture of fibroblasts with an established rat mast cell line (RMC-1) was used to explore the hypothesis of whether mast cells through gap junctional intercellular communications guide fibroblasts in promoting excessive scarring., Methods: Human dermal fibroblasts were cultured alone or co-cultured with RMC-1 cells as is or with either blocked gap junctional intercellular communications or devoid of cytoplasmic granules. Collagen synthesis was analyzed by dot blot analysis; immunohistology identified myofibroblasts, and a cell migration assay measured fibroblast locomotion., Results: Fibroblasts co-cultured with RMC-1 cells transformed into myofibroblasts, had increased collagen synthesis, and showed retarded cell migration. In contrast, RMC-1 cells unable to form gap junctional intercellular communications were similar to fibroblasts alone, failing to promote these activities. Degranulated RMC-1 cells were as effective as intact RMC-1 cells., Conclusions: Mast cells induce fibroblast activities associated with hypertrophic scarring through gap junctional intercellular communications. Eliminating the mast cell or its gap junctional intercellular communications with fibroblasts may be a possible approach in preventing hypertrophic scarring or reducing fibrotic conditions.

Background: The physiopathogenesis of proliferative scarring in human skin is not well understood. Furthermore, knowledge of the precise mechanisms of action for physical treatment modalities is limited. Compression garments, occlusive/adhesive skin taping, and silicone gel sheets are applied to form an occlusion on the scar surface, reduce tension, and/or increase pressure on the scar itself. The mechanisms by which the external or superficial actions of these treatments cause remission of a protruding scar may be related to mechanoreceptor (nociceptor and cellular mechanoreceptor) responses., Methods: Basic research studies about mechanoreceptor-related (nociceptors and cellular mechanoreceptors, separately) events are reviewed and discussed based on proliferative scarring background. Scar management-related studies were corrected from the standpoint of mechanotransduction mechanisms. The methodologic quality of the clinical trials and basic studies was evaluated and reviewed., Results: It was suggested that many of the physical scar management methods, including compression therapy, silicone therapy, adhesive tape, and occlusive dressing therapy, are related to mechanotransduction mechanisms., Conclusions: A unifying perspective of basic research findings and clinical observations may be obtained by considering the mechanoreceptor-related events in scar management. Moreover, a precise understanding of the roles that cellular mechanoreceptors and mechanosensitive nociceptors play in proliferative scarring may lead to the development of innovative treatment strategies and new pharmacologic therapies targeting cellular mechanoreceptors and mechanosensitive nociceptors in fibroproliferative diseases.

Background: Keloids and hypertrophic scars can be uncomfortable, disfiguring, and aesthetically undesirable. Anecdotal reports suggest that low-dose intralesional fluorouracil can be used to treat these undesirable scars., Methods: Using a prospective case series protocol, both keloid and hypertrophic scar patients were included. Keloid patients underwent excision followed by a series of treatments with intralesional 5-fluorouracil into the healing scar to prevent recurrence (n = 32). The hypertrophic scar patients were treated with the same series of injections without scar excision to both control symptoms and improve scar appearance (n = 21). The primary outcome measures were scar volume and a symptom questionnaire. Patients were followed for 1 year after completing the injection treatments., Results: In the keloid group, the recurrence rate was 19 percent at 1-year follow-up for this group of patients who had failed previous corticosteroid injection therapy. In the hypertrophic scar group, 14 percent did not respond to the series of injections. In this group, there was a median volume decrease of 50 percent maintained for 1 year after injection therapy was terminated., Conclusions: Intralesional fluorouracil is a safe and effective means of controlling problem scars in terms of both recurrence and symptom control. Benefits were maintained for at least 1 year after completion of therapy. Intralesional 5-fluorouracil should be considered another option for patients suffering from problematic scars.

Background: Expression of connexins and other constituent proteins of gap junctions along with gap junctional intercellular communication are involved in cellular development and differentiation processes. In addition, an increasing number of hereditary skin disorders appear to be linked to connexins. Therefore, in this report, the authors studied in vitro gap junctional intercellular communication function and connexin expression in fibroblasts derived from keloid and hypertrophic scar patients., Methods: Fibroblasts harvested from each of six keloid and hypertrophic scar patients were used for this study. Gap junctional intercellular communication function was investigated using the gap fluorescence recovery after photobleaching method, and expression of connexin proteins was studied using quantitative confocal microscopic analyses., Results: Compared with normal skin, a decreased level of gap junctional intercellular communication was seen in fibroblasts derived from hypertrophic scar tissue, whereas an extremely low gap junctional intercellular communication level was detected in fibroblasts derived from keloid tissue. We also detected little connexin 43 (Cx43) protein localized in fibroblasts derived from keloids. Moreover, Cx43 protein levels were much lower in fibroblasts derived from hypertrophic scars than in those derived from normal skin., Conclusions: The authors' data suggest that the loss of gap junctional intercellular communication and connexin expression may affect intercellular recognition and thus break the proliferation and apoptosis balance in fibroblasts derived from keloid and hypertrophic scar tissue.

Background: How a scar is managed postoperatively influences its cosmetic outcome. After suture removal, scars are susceptible to skin tension, which may be the trigger for hypertrophic scarring. Paper tape to support the scar may reduce multidirectional forces and prevent hypertrophic scarring., Methods: Seventy patients who had undergone cesarean section at the Royal Brisbane and Women's Hospital were randomized to treatment and control groups. Patients in the control group received no postoperative intervention. Patients in the treatment group applied paper tape to their scars for 12 weeks. Scars were assessed at 6 weeks, 12 weeks, and 6 months after surgery using ultrasound to measure intradermal scar volume. Scars were also assessed using the International Clinical Recommendations., Results: Paper tape significantly decreased scar volume by a mean of 0.16 cm3, (95 percent confidence interval, 0.00 to 0.29 cm3). At 12 weeks after surgery, 41 percent of the control group developed hypertrophic scars compared with none in the treatment group (exact test, p = 0.003). In the treatment group, one patient developed a hypertrophic scar and four developed stretched scars only after the tape was removed. The odds of developing a hypertrophic scar were 13.6 times greater in the control than in the treatment group (95 percent confidence interval, 3.6 to 66.9). Of the 70 patients randomized, 39 completed the study. Four patients in the treatment group developed a localized red rash beneath the tape. These reactions were minor and transient and resolved without medical intervention., Conclusions: The development of hypertrophic and stretched scars in the treatment group only after the tape was removed suggests that tension acting on a scar is the trigger for hypertrophic scarring. Paper tape is likely to be an effective modality for the prevention of hypertrophic scarring through its ability to eliminate scar tension.

Wound contraction in humans has both positive and negative effects. It is beneficial to wound healing by narrowing the wound margins, but the formation of undesirable scar contracture brings cosmetic and even functional problems. The entire mechanism of wound healing and scar contracture is not clear yet, but it is at least considered that both the fibroblasts and the myofibroblasts are responsible for contraction in healing wounds. The myofibroblast is a cell that possesses all the morphologic and biochemical characteristics of both a fibroblast and a smooth muscle cell. Normally, the myofibroblasts appear in the initial wound healing processes and generate contractile forces to pull both edges of an open wound until it disappears by apoptosis. But as an altered regulation of myofibroblast disappearance, they remain in the dermis and continuously contract the scar, eventually causing scar contracture. In this research, to compare and directly evaluate the influence on scar contracture of the myofibroblast versus the fibroblast, dermal tissues were taken from 10 patients who had highly contracted hypertrophic scars. The myofibroblasts were isolated and concentrated from the fibroblasts using the magnetic activating cell-sorting column to obtain the myofibroblast group, which contained about 28 to 41 percent of the myofibroblasts, and the fibroblast group, which contained less than 0.9 percent of the myofibroblasts. Each group was cultured in the fibroblast-populated collagen lattice for 13 days, and the contraction of the collagen gel was measured every other day. In addition, they were selectively treated with tranilast [N-(3',4'-dimethoxycinnamoyl) anthranilic acid] to evaluate the influence on the contraction of the collagen gel lattice. During the culture, the myofibroblast group, compared with the fibroblast group, showed statistically significant contraction of the collagen gel lattice day by day, except on the first day, and only the myofibroblast group was affected by tranilast treatment, showing significant inhibition of gel contraction. By utilizing an in vitro model, the authors have demonstrated that myofibroblasts play a more important role in the contracture of the hypertrophic scar.

Silicone gel and silicone occlusive sheeting are widely used at present for the treatment of hypertrophic and keloid scars, without any scientific explanation as to their mode of action. In a recent paper the possibility was raised that static electricity generated by friction-activated silicone sheeting could be the reason for this effect, and that it can, with time, cause involution of hypertrophic and keloid scars. The objective of this study was to test this hypothesis and to observe whether a continuous and also an increased negatively charged static-electric field will shorten the treatment period. A device to implement these requirements gradually evolved over a 5-year period. A number of prototypes were tested until the final product was attained. Some of the patients in this study were treated initially with a silicone sponge inserted in the cushion. Later this version was changed to the final design described herein. A silicone cushion was developed with the purpose of increasing a negative static-electric charge to accelerate the regression process. The cushion is custom-made using a silicone occlusive sheeting envelope of 0.75-mm thickness, which does not deteriorate with use, and is partially filled with high viscosity silicone oil. Its edges are sealed, and its size is designed to extend a little beyond the scarred area. Static electricity readings, generated by activating the cushion by pumping action with the fingers, stretching or deforming the cushion, are invariably much higher when compared with those obtained with silicone occlusive sheeting and silicone gel sheeting. The interaction between the negatively charged ions of the cushion and the ionic charges of the tissue fluids may be the critical factor in achieving hypertrophic and keloid scars involution. Of the 30 patients enrolled in the study, 3 patients dropped out. Treatment with the silicone cushions yielded 63.3 percent cessation of itching and burning followed by pallor and flattening of the scar, some markedly so, over a few weeks to 6-month period. An additional 26.6 percent had their scars resolved in up to 12 months of treatment. Good contact of the cushion over the scar has been shown to be important in this clinical trial, and much creativity is needed for making elastic strap bindings that ensure this contact. The clinical trials extended over a 12-month period. Ten patients (33.3 percent) who had recalcitrant scars with little response to the use of the silicone cushion were given intralesional corticosteroid injections, in addition to the continued use of the cushion, resulting in a fairly rapid resolution of these scars over a period of months to a year.

Longitudinal stretching of wounds that cross the relaxed skin tension lines appears to be the stimulus that causes the body to form hypertrophic scars. Control or elimination of such stretching forces by the long-term use of paper tape, beginning at 2 weeks, has been effective in preventing such hypertrophic scarring.