Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets.

Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment.

A systematic review of the management of postoperative scars with silicone gel-based products in randomized controlled trials.

Although postoperative scarring may be considered a cosmetic concern, it can greatly impact a patient's quality of life. This extends beyond psychosocial burden influenced by hypertrophic scars and keloids, as patients also experience discomfort and pain. This systematic review evaluates the efficacy of silicone gel (SG)-based products in preventing postoperative abnormal scar formation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a PubMed search was performed to find randomized, controlled trials investigating the effect of SG-based products on postoperative wound healing. The search yielded 359 publications, but only 30 studies published between 1991-2022 were found to fit the inclusion criteria. Outcomes were extracted from the literature and subsequent quality and risk of bias assessments were performed. Most studies indicated improvement of at least one quality of the scar with the use of SG-based products. The greatest potential variable increasing bias was an inadequate control group. Studies also suffered from small sample sizes, use of unvalidated scar assessment scales, lack of double-blinding, and short follow-up periods. Overall, SG-based products demonstrated potential in preventing abnormal scar formation during postoperative healing, but further studies are required to validate the results of current literature.

Comparison of LeniScar Silicone Stick (AnsCare) With Traditional Silicone Gel (Dermatix Ultra) in Wound Scar Prevention and Removal.

BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.

Excision and adjuvant treatment to prevent keloid recurrence. - a systematic review of prospective, clinical, controlled trials.

Keloids are defined as the formation of collagen-rich scar tissue extending beyond the original lesion. Not all keloids respond to conventional treatment with intralesional triamcinolone injections. Recurrence of keloids after primary excision is reported in almost 100% of cases and should therefore always be followed by adjuvant treatment. Currently, consensus on preferred adjuvant treatment in relation to keloid excision is lacking. This study seeks to systematically review evidence on the efficacy of adjuvant treatments in relation to keloid excision. A systematic literature review was conducted on PubMed. Titles, abstracts, and articles were screened and sorted according to defined inclusion- and exclusion criteria. Each study was evaluated according to the Oxford Centre for Evidence-Based Medicine, OCEBM, Levels of Evidence by two independent authors. Seven studies were eligible. Adjuvant treatment methods included intralesional triamcinolone injection, radiotherapy, silicone gel, pressure therapy, verapamil hydrochloride and 5-fluorouracil. While all the included studies reported promising results, two studies showed that minimizing dosages when treating with radiotherapy or triamcinolone should be considered to avoid adverse events. However, a high risk of bias was found in all the included studies.

Mechanomodulatory biomaterials prospects in scar prevention and treatment.

Scarring is a major clinical issue that affects a considerable number of patients. The associated problems go beyond the loss of skin functionality, as scars bring aesthetic, psychological, and social difficulties. Therefore, new strategies are required to improve the process of healing and minimize scar formation. Research has highlighted the important role of mechanical forces in the process of skin tissue repair and scar formation, in addition to the chemical signalling. A more complete understanding of how engineered biomaterials can modulate these mechanical stimuli and modify the mechanotransduction signals in the wound microenvironment is expected to enable scar tissue reduction. The present review aims to provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment. Furthermore, a broad overview of current challenges and future perspectives of promising mechanomodulatory biomaterials for this application are provided. STATEMENT OF SIGNIFICANCE: Scarring still is one of the biggest challenges in cutaneous wound healing. Beyond the loss of skin functionality, pathological scars, like keloids and hypertrophic, are associated to aesthetic, psychological, and social distress. Nonetheless, the understanding of the pathophysiology behind the formation of those scars remains elusive, which has in fact hindered the development of effective therapeutics. Therefore, in this review we provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment.

[Prevention and treatment of keloids].

Keloids are pathological scars extending beyond the initial wound's natural borders. The condition occurs as a result of impaired wound healing with excessive collagen deposition. Keloid scars frequently recur, rarely regress, and have a tendency to grow over time. They are aesthetically disfiguring and can be devastating for patients, both physically and emotionally. This review finds that prevention and early intervention are essential for good results. Treatment is often challenging. There are no standardized management guidelines currently available but a combinational therapeutic approach appears to be beneficial.

The use of fluid silicone gels in the prevention and treatment of hypertrophic scars: a systematic review and meta-analysis.

BACKGROUND: Silicone products, either as a sheet or in fluid form, are universally considered as the first line therapy in the prevention and treatment of hypertrophic scars and keloids. However, the study results have been questioned by different authors and there has never been a large systematic synopsis published on the efficacy of fluid silicone gels. This systematic review aims to elucidate the available evidence of the results obtained by fluid silicone gels and present a complete and comprehensive overview of the available literature as well as a meta-analysis of the pooled data. METHODS: A systematic search for articles concerning the use of silicone gel in the treatment and prevention of scars was performed on 3 different databases (Pubmed, Embase and Cochrane library) according to the PRISMA statement. Only RCT's were included. Qualitative assessment was done by 2 separate reviewers using the Cochrane risk of bias (RoB 2) assessment tool. Revman 5.4.1 software was used for meta-analysis. RESULTS: The search yielded 507 articles. Two articles were identified through other sources. After deduplication and removal of ineligible records, 340 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 18 articles were included. A meta-analysis comparing fluid silicone gel to no treatment or placebo gels was conducted. CONCLUSION: Studies on the effects of liquid silicone gels on hypertrophic scars are numerous and this systematic review shows that the use of liquid silicone gels is associated with both a prophylactic and a curative effect on scars. However, a considerable amount of the available 'high evidence' trials are at a high risk for bias and it is uncertain whether or not the effects of silicone gels are comparable to silicone sheets and if the additional components present in many silicone gels are partially responsible for their scar improving capacity.

Surgical considerations in skin of colour: minimizing pathological scars.

In most surgeries, the primary aim, for both surgeons and patients, is the success of the operation being undertaken. A secondary aim is for optimal wound healing with minimal scar formation. The normal wound-healing process involves four distinct but overlapping stages: haemostasis, inflammation, proliferation and remodelling. In some patients, the cellular process involved in the proliferation and remodelling stages can be deranged, resulting in the formation of hypertrophic or keloid scars, a phenomenon more frequently seen in skin of colour. The first report of excessive scarring is thought to be the Smith papyrus about 1700 BC. In the 20th century, both Mancini and Quaife (in 1962) and Peacock et al. (in 1970) classified excessive scarring into hypertrophic and keloid scar formation. Clinicians can minimize the risk of these pathological scars developing by using good preoperative, perioperative/intraoperative and postoperative surgical practices. This paper reviews the wound-healing processes in association with good surgical principles and practice, discusses how implementing these principles in practice helps in this prevention and management of pathological surgical scars such as hypertrophic scars and keloid scars. and offers a practical step-by-step clinical guide that can be used by any clinician.

Screw-loaded compression device for auricular keloid.

Pressure therapy is widely used in the management of keloid mass and for preventing postexcision recurrence of earlobe keloid. Although various types of compression devices are available, the pressure applied by these devices is uncontrolled and associated with the risk of pressure necrosis. This article presents a novel design for a compression device with threaded connectors to control the amount and direction of the pressure applied on the keloid mass.

A Review of Hypertrophic Scar and Keloid Treatment and Prevention in the Pediatric Population: Where Are We Now?

Significance: This body of work gives a concise and comprehensive overview for the clinician and scientist on the latest treatment modalities for hypertrophic scars (HTS) and keloids in the pediatric population, as well as the most promising methods of prevention currently being investigated. This review will serve as a guide to the clinician for treatment selection and as an efficient tool for the scientist to achieve a comprehensive overview of the scientific literature to guide their future experiments aimed at pathologic scar prevention. Recent Advances: Current studies in the literature suggest carbon dioxide (CO2) laser and E-light (bipolar radiofrequency, intense pulsed light, and cooling) are two of the most effective treatment modalities for HTS, while surgical excision+CO2 laser+triamcinolone injection was one of the most successful treatments for keloids. In animal models, drug impregnated electrospun nanofiber dressings offer encouraging results for HTS prevention, while Kelulut honey showed promising results for keloid prevention. Critical Issues: Treatment outcome reproducibility is hindered by small cohorts of patients, inadequate-follow up, and variability in assessment tools. Prevention studies show multiple ways of achieving the same result, yet fall short of complete prevention. Furthermore, some studies that have purported full prevention have not been validated. Future Directions: To establish a standard of care, large clinical trials of the most successful modalities in small cohorts are needed. The key for prevention will be validation in animal models of the most successful methods, followed by translational and clinical studies.

Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid.

Keloids are a common form of pathologic wound healing and are characterized by an excessive production of extracellular matrix. This study examined the major contributing mechanism of human keloid pathogenesis using transcriptomic analysis. We identified the upregulation of mitochondrial oxidative stress response, protein processing in the endoplasmic reticulum, and TGF-ß signaling in human keloid tissue samples compared to controls, based on ingenuity pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Electron microscopic examinations revealed an increased number of dysmorphic mitochondria and expanded endoplasmic reticulum (ER) in human keloid tissue samples than that in controls. Western blot analysis performed using human tissues suggested noticeably higher ER stress signaling in keloids than in normal tissues. Treatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, significantly decreased scar formation in rabbit models, compared to normal saline and steroid injections. In summary, our findings demonstrate the contributions of mitochondrial dysfunction and dysregulated ER stress signaling in human keloid formation and the potential of TUDCA in the treatment of keloids.

Dicas em Saúde: Queloide

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Asporin inhibits collagen matrix-mediated intercellular mechanocommunications between fibroblasts during keloid progression.

Keloids are fibrotic lesions that grow unceasingly and invasively and are driven by local mechanical stimuli. Unlike other fibrotic diseases and normal wound healing, keloids exhibit little transformation of dermal fibroblasts into α-SMA+ myofibroblasts. This study showed that asporin is the most strongly expressed gene in keloids and its gene-ontology terms relate strongly to ECM metabolism/organization. Experiments with human dermal cells (HDFs) showed that asporin overexpression/treatment abrogated the HDF ability to adopt a perpendicular orientation when subjected to stretching tension. It also induced calcification of the surrounding 3D collagen matrix. Asporin overexpression/treatment also prevented the HDFs from remodeling the surrounding 3D collagen matrix, leading to a disorganized network of thick, wavy collagen fibers that resembled keloid collagen architecture. This in turn impaired the ability of the HDFs to contract the collagen matrix. Asporin treatment also made the fibroblasts impervious to the fibrous collagen contraction of α-SMA+ myofibroblasts, which normally activates fibroblasts. Thus, by calcifying collagen, asporin prevents fibroblasts from linearly rearranging the surrounding collagen; this reduces both their mechanosensitivity and mechanosignaling to each other through the collagen network. This blocks fibroblast activation and differentiation into the mature myofibroblasts that efficiently remodel the extracellular matrix. Consequently, the fibroblasts remain immature, highly proliferative, and continue laying down abundant extracellular matrix, causing keloid growth and invasion. Notably, dermal injection of asporin-overexpressing HDFs into murine wounds recapitulated keloid collagen histopathological characteristics. Thus, disrupted interfibroblast mechanocommunication may promote keloid progression. Asporin may be a new diagnostic biomarker and therapeutic target for keloids.