Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-β)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-β/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation. In addition, optic atrophy 1 (OPA1)-mediated mitochondrial fusion contributes to fibroblast proliferation, and TGF-β/Smad3 axis and the Notch1 pathway facilitate OPA1-mediated mitochondrial fusion. Thus, the aim of this study was to investigate whether drugs targeting TGF-β/Notch interaction via Smad3 suppressed fibroblast proliferation to attenuate HS formation through OPA1-mediated mitochondrial fusion. We found that the TGF-β pathway, Notch pathway, and TGF-β/Notch interaction via Smad3 were inhibited by pirfenidone, the gamma- secretase inhibitor DAPT, and SIS3 in human keloid fibroblasts (HKF) and an HS rat model, respectively. Protein interaction was detected by co-immunoprecipitation, and mitochondrial morphology was determined by electron microscopy. Our results indicated that pirfenidone, DAPT, and SIS3 suppressed the proliferation of HKFs and attenuated HS formation in the HS rat model by inhibiting TGF-β/Notch interaction via Smad3. Moreover, pirfenidone, DAPT, and SIS3 hindered OPA1-mediated mitochondrial fusion through inhibiting TGF-β/Notch interaction, thereby suppressing the proliferation of HS fibroblasts and HS formation. In summary, these findings investigating the effects of drugs targeting TGF-β/Notch interaction on HS formation might lead to novel drugs for the treatment of HS formation.

Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re-epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu-TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu-TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5-fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co-delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu-TSs not only promote macrophage phenotype-switching to inhibit inflammation by interleukin-related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen-related pathways. Therefore, TA/Fu-TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype-switching and anti-fibrosis effect.

OBJECTIVE: Platelet-rich plasma (PRP) is widely used for wound healing in medical care because of the numerous growth factors it contains. Traditionally, donor sites are left to heal with a primary dressing so wounds are not left open. However, a delay in healing accompanied by pain at a donor site is often seen. This study primarily throws light on the use of autologous PRP over split-thickness skin graft (STSG) donor sites to promote healing and reduce pain.
METHODS: The patients enrolled in this study in 2018-2019 were divided into two groups: the intervention group received autologous PRP applied topically at the donor site; in the control group, the wound was dressed traditionally. Pain scales were measured in the immediate postoperative period at six hours, 10 hours and 16 hours. The dressing was opened on the postoperative day 14 and observed for healing by an independent observer.
RESULTS: A total of 100 patients were included in the study. Patients in the PRP group showed statistically significant faster healing at postoperative day 14 compared with the control group (p<0.05), who required dressings for 3-4 weeks postoperatively. Pain scale scores in the postoperative period were significantly less in the PRP group at six hours postoperatively compared with the control group (p<0.05). There was a reduced incidence of hypertrophic scar formation in the small number of patients in the PRP group who had developed hypertrophic scar previously.
CONCLUSIONS: Application of PRP is a safe, cost-effective and easy method to achieve faster healing in graft donor site areas that are troublesome to both patients and doctors. It also reduces postoperative pain at donor sites. The authors recommend PRP is used more often in the management of donor sites for STSGs.

Chronic pruritus carries a significant burden of disease and is associated with a negative impact on quality of life. African Americans are disproportionately burdened by chronic pruritic disorders, including but not limited to atopic dermatitis, prurigo nodularis, inflammatory scalp dermatoses, pathologic scarring, and HIV-related dermatoses. Racial differences in skin structure and function may contribute to the pathogenesis of itch in African Americans. Itch perception and response to treatment in African Americans remain understudied and not well understood. As such, there is a large unmet need with regard to the knowledge and management of pruritus in African Americans. This review highlights notable differences in the epidemiology, pathophysiology, genetic predisposition, clinical presentation, and response to treatment for select pruritic skin conditions. By addressing itch as an unmet need in African Americans, we hope to improve patient outcomes and lessen disparities in dermatologic care.

Transforming growth factor β (TGF-β) is a growth factor presenting important functions during tissue remodeling and hypertrophic scar (HS) formation. However, the underlying molecular mechanisms are largely unknown. In this study, we identified thrombospondin-4 (TSP-4) as a TGF-β1 target that essentially mediates TGF-β1-induced scar formation both in vitro and in vivo. The expression of TSP-4 was compared on both mRNA and protein levels between hypertrophic scar fibroblasts (HSFs) and normal skin fibroblast (NFs) in response to TGF-β1 treatment. Two signaling molecules, Smad3 and p38, were assessed for their importance in regulating TGF-β1-mediated TSP-4 expression. The significance of TSP-4 in controlling TGF-β1-induced proliferation, invasion, migration, and fibrosis in HSFs was analyzed by knocking down endogenous TSP-4 using small hairpin RNA (shRNA) (TSP-4 shRNA). Finally, a skin HS model was established in rats and the scar formation was compared between rats treated with vehicle (saline), TGF-β1, and TGF-β1 + TSP-4 shRNA. The TSP-4 level was significantly higher in HSFs than in NFs and TGF-β1 more potently boosted TSP-4 expression in the former than in the latter. Both Smad3 and p38 essentially mediated TGF-β1-induced TSP-4 expression. TSP-4 shRNA significantly suppressed TGF-β1-stimulated proliferation, invasion, migration, or fibrosis of HSFs in vitro and drastically improved wound healing in vivo. TGF-β1, by activating both Smad3 and p38, induces TSP-4, which in turn not only presents a positive feedback regulation on the activation of Smad3 and p38, but also essentially mediates TGF-β1-induced HS formation. Targeting TSP-4 thus may benefit HS treatment.

OBJECTIVE: Significant functional impairment and psychological burden may result from poor scar quality and its impact on patient\'s quality of life has been well-established. It is important to identify measures to reduce the risk of surgical complications.
METHODS: 212 patients undergoing dermatological surgery were recruited from March 2011 to February 2014. Their age, sex, surgical site, closure type, defect size (length and width), scar length, number of deep sutures, suture type and size were recorded. The patients were followed up at 6 weeks and 6 months for complications including abscess formation, granuloma formation, scar spreading, suture spitting and hypertrophic scar formation.
RESULTS: At 6 weeks complications included suture spitting (14%), granuloma (11%), scar spreading (7%), hypertrophic scarring (3%) and abscess formation (1%), and at 6 months; scar spreading (17%), hypertrophic scarring (2%) and suture spitting (1%). In our multivariate analysis there were no predictors for spreading or spitting at 6 weeks, and only the defect size width was a predictor for granulomas in the stepwise analysis. For scar spreading at 6 months, younger age, site (trunk or limbs), higher number of deep sutures and surgeon were independent predictors (P < 0.0001 for the model).
CONCLUSIONS: Complications following dermatological surgery are low and tend to resolve with time, except for scar spreading. The surgeon who experienced more complications was placing sutures more superficially to the skin surface and was throwing more knots per closure; factors that we did not record in our study and merit further study.