Keloid Research Articles

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids.

Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods. Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids. Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments. Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular. Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

A Manually Curated Database and Analysis Platform of Cell Markers of Scars

Pathologic scar, a common disease involving dermal fibrotic disorder caused by an aberrant wound-healing response, afflicts over 100 million people every year worldwide. Unlike normal scars, pathologic scars, such as hypertrophic or keloid scars, can be highly disfiguring and have major psychological impact on the patients ( Trace et al., 2016 Trace A.P. Enos C.W. Mantel A. Harvey V.M. Keloids and hypertrophic scars: a spectrum of clinical challenges. Am J Clin Dermatol. 2016; 17: 201-223 Crossref PubMed Scopus (65) Google Scholar ). Molecular therapies provide potential solutions for the disease when it could not be improved by current available therapies.

OMICS Approaches Evaluating Keloid and Hypertrophic Scars.

Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of "omics" approaches to study abnormal scars and provide examples of genomics, transcriptomics, proteomics, epigenomics, and metabolomics. The benefits of "omics" approaches are that they allow for high-throughput studies and the analysis of 100s to 1000s of genes and proteins with the accumulation of large quantities of data. Currently in the field, there is a lack of "omics" review articles describing pathological scars. In this review, we summarize genome-wide linkage analysis, genome-wide association studies, and microarray data to name a few omics technologies. Such data can provide novel insights into different molecular pathways and identify novel factors which may not be captured through small-scale laboratory techniques.

Postoperative weakness and anesthetic-associated rhabdomyolysis in a pediatric patient: a case report and review of the literature

BackgroundAnesthesia-associated rhabdomyolysis is a rare complication of surgery that causes postoperative myalgia, weakness, and potential renal failure if not managed promptly. Predisposing conditions that may lead to this complication include muscular dystrophies and myopathies.Case presentationThis rare case describes a pediatric non-Indigenous Australian patient developing this complication, with no known predisposing risk factors, and no clear etiology. A 9-year-old child with a background of asthma underwent an elective removal of keloid scar on her chest wall. The procedure was brief and uncomplicated, with an uneventful induction of anesthesia. During the emergence period, she developed acutely raised airway pressures with bronchospasm and laryngospasm requiring the use of salbutamol and suxamethonium with good effect. In the initial postoperative period, the patient complained of generalized myalgia and muscle weakness and was unable to mobilize independently. There was transient recovery to normal function; however, a recurrence of symptoms the following day with associated myalgias warranted admission to hospital. She was found to have rhabdomyolysis that was managed conservatively with a full recovery of several weeks. She was thoroughly investigated for any underlying cause, including genetic testing for malignant hyperthermia susceptibility (she had a variant of unknown significance but was negative for the known genetic abnormalities that cause malignant hyperthermia).ConclusionThis case report demonstrates the importance of considering anesthesia-associated rhabdomyolysis as a differential for acute postoperative weakness, and outlines an investigative approach. To the best of our knowledge, it is the first case described in the pediatric literature to report biphasic progression of symptoms.

The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release.

Keloid scarring is an abnormal scar disease characterised by excessive proliferation of fibroblasts and over-deposition of collagen during wound healing. Although various treatments for keloid scars have been developed, preventive medicine is believed to be a promising strategy. The skin barrier limits the gentle topical administration of medicaments such as creams and hydrogel dressings, resulting in reduced therapeutic efficacy. In recent years, microneedles (MNs) have been regarded as an appreciable device for topical administration without inducing side effects, and they are painless and do not cause bleeding. In this study, an MN patch with controlled transdermal dual-drug release was developed to achieve combinatory treatment of keloid scars using a heterogeneous gelatin-structured composite MN. Gelatin hydrogel was used as a substrate to load gallic acid (GA) and quercetin-loaded amphiphilic gelatin nanoparticles to fabricate dual-drug heterogeneous composite MNs. The results of the insertion test and mechanical properties of the MNs showed that the heterogeneous composite MN patches could be self-pressed into the stratum corneum and control dual-drug release at different time periods. GA was released at an earlier stage to retard the proliferation of fibroblasts, and quercetin was released at a later stage as a strong antioxidant to erase the generation of reactive oxygen species. Furthermore, real-time quantitative polymerase chain reaction data indicated that the gene expression of fibroblasts (such as Col I and III) was downregulated in the dual-drug system. The above results demonstrate that using heterogeneous composite MNs with the combination of dual-drug pharmacology is beneficial for preventing keloid scar formation.

An improved explants culture method: Sustainable isolation of keloid fibroblasts with primary characteristics.

Keloid (KD) is a complex fibroproliferative disease, but the exact mechanisms underlying keloid pathogenesis remain to be elucidated. The primary keloid fibroblasts (KFs) culture in vitro has always been a fundamental measure to study the pathogenesis of keloid. However, the traditional primary culture methods have some limitations, such as a long culture cycle, low specimen utilization rate and so on. Improve the keloid explants culture method sts. We proposed an improved new "explants multiple culture method"-reusing keloid explants for primary culture and harvesting the primary KFs in specific culture times. Meanwhile, the purity, proliferation, apoptosis, migration, invasion, extracellular matrix synthesis, and some fibrosis and inflammation-related proteins of KFs obtained from the first, fifth, and tenth explants cultures were detected. The results showed that the culture cycle of this new method (Cell Isolation: 2.67 ± 0.86 days, Explants removal: 8.83 ± 0.79 days, Cell Passage: 15.17 ± 1.39 days) was significantly shorter than that of the traditional method (Cell Isolation: 8.67 ± 1.84 days, Explants removal: 17.67 ± 2.17 days, Cell Passage: 22.67 ± 1.84 days). No significant difference was observed between the phenotypes of the fibroblasts obtained from the first explants culture and cultures less than 10 times (p > 0.05). Taken together, this study provides an effective method for the primary culture of KFs with a higher specimen utilization rate and shorter culture cycle. This method breaks through the limitation of traditional explants culture requiring a large number of keloid specimens and provides a rich source of KFs for the study of keloid.

Brocq's geometric phagedena over penis with keloidal scars.

Pyoderma gangrenosum is a rare neutrophilic inflammatory skin disorder commonly seen over lower limbs. Involvement of penile area is rare. We report this rare case of occurrence of ulcerative type of pyoderma gangrenosum over penis with pustular type elsewhere over the body, healing with keloids in an immunocompetent young man with no systemic associations.

Comparative Efficacy of Intralesional Triamcinolone Acetonide and 5-Fluorouracil for Keloid Scars.

Intralesional triamcinolone acetonide (TAC; a synthetic corticosteroid) and 5-fluorouracil (5-FU; a cytotoxic chemotherapy drug) are the medications most commonly used to treat keloid scars. We investigated the clinical efficacy of TAC compared with 5-FU. We included 40 patients in the study and divided them into two equal groups ( n = 20 Group A; n = 20 Group B). Group A patients received 4 mg/cm 2 or 0.1 ml/cm 2 of intralesional TAC (40 mg/ml) at 3-week intervals. Group B patients received 10 mg/cm 2 or 0.2 ml/cm 2 of intralesional 5-FU (50 mg/ml) at 3-week intervals. We assessed the scar using the Vancouver Scar Scale (VSS), visual analog scale (VAS), and patient satisfaction score (PSS). We found that Group A patients had a lower VAS than Group B patients (2.09 vs. 3.18). We saw a reduction in the VSS in both treatment arms; however, we found that Group B patients had a more marked reduction in the VSS compared with Group A patients (2.57 vs. 2.68). The PSS was higher in Group A than in Group B (1.97 vs. 1.78). We concluded that intralesional 5-FU elicits a better response than intralesional TAC. Although 5-FU is less well tolerated and has more side effects than TAC, we found that 5-FU was more effective in resolving keloid scars. Notably, the PSS was higher in the TAC group, but the VSS and VAS were better in Group B.

Laser therapy for treating hypertrophic and keloid scars.

Laser therapy for treating hypertrophic and keloid scars.

Micropipette Tip-Guarded Needle for Intralesional Therapy in Keloid and Hypertrophic Scar

Micropipette Tip-Guarded Needle for Intralesional Therapy in Keloid and Hypertrophic Scar

Keloid: Genetic susceptibility and contributions of genetics and epigenetics to its pathogenesis.

Keloid, characterized by fibroproliferative disorders of the skin, can be developed in people of different genders, ages and ethnicities. Keloid can appear in any part of the body but are especially common on the earlobe, upper torso and triangular muscle. The genetic heterogeneity and susceptibility of KD (keloid) vary among different races and ethnicities. Studies have found that multiple loci on multiple chromosomes are associated with the pathogenesis of KD, and specific gene variants may also be involved. Despite multiple investigations attempting to uncover the aetiology of keloid formation, the genetic mechanism of keloid formation remains unknown. To establish a foundation for a better understanding of the genetics and epigenetics of keloids, we have evaluated and summarized current studies which are mostly related to heredity, genetic polymorphisms, predisposing gene, DNA methylation and non-coding RNA. We also discussed the problems and potential of genetic and epigenetic investigations of keloids, with the goal of developing new therapeutic approaches to enhance the prognosis of keloid patients.

32561 Development and validation of a new, disease-specific quality of life assessment instrument for patients with keloid disorder

Background: Keloid disorder (KD) is a relatively understudied condition that causes significant impairment in the quality of life (QoL) of patients; however, adequate tools to assess QoL in patients with KD do not exist.

Radiation-induced FAP + fibroblasts are involved in keloid recurrence after radiotherapy.

Background: Keloid scars (KSs), which are composed of abnormal hyperplastic scar tissue, form during skin wound healing due to excessive fibroblast activation and collagen secretion. Although surgical resection and radiation therapy are used to prevent recurrence, KS recurrence rates range from 15 to 23%, and the underlying mechanism is unclear. Methods: To elucidate the mechanism of keloid recurrence, we established a PDX model and the grafts remained for over 20 weeks after transplantation on the bilateral backs of the NCG mice. Results: RNA-seq revealed that KS tissue gene expression was highly consistent before and after transplantation. Then, one side of the KS graft was irradiated with electron beam therapy (10 Gy), significant increases in vimentin and fibroblast activation protein alpha (FAP) expression were observed after irradiation and were accompanied by severe microvascular destruction. Surprisingly, 4 weeks after irradiation, significantly increased recurrence was observed with increased FAP + tissue and cell cycle regulator expression, resulting in a remarkable altered graft volume. Moreover, irradiation-induced FAP upregulation markedly facilitated radiation resistance and increased cell cycle progression, decreased senescence, and increased energy production. Conclusion: Our findings revealed that irradiation causes increased abundance of FAP + cells, which was associated with cell proliferation and delayed cellular senescence, accompanied by ATP production.

Irradiation Methods for Accurate Dose Delivery to Postoperative Keloid Scars With Minimal Normal Tissue Exposure Using TomoTherapy: A Phantom Study.

We aimed to clarify the TomoTherapy irradiation method for accurate dose delivery to the postoperative ear keloid with minimal exposure. An electron beam of Elekta synergy and static and helical photon beams of TomoTherapy were delivered to the auricle and lobe of an anthropomorphic phantom compensated using a soft rubber bolus. The doses to the ear surface and the eyeballs and thyroid were measured using radiochromic film and glass dosimeters, respectively. Using static, helical, and electron beams, the respective doses to the ear surface were 97.9%, 103.0%, and 91.7% of the prescribed dose; the respective doses to the thyroid were 0.6, 0.8, and 2.4 cGy; the respective doses to the left eyeball were 3.3, 6.9, and 2.7 cGy. The static beam of the TomoTherapy can be safely used for treating ear keloids, while ensuring target dose. The helical photon beam spreads out the low-dose exposure.

Study the efficacy of intralesional pentoxifylline versus triamcinolone acetonide in keloid scars patients

Keloids are prevalent fibro-proliferative tumors, and treating them is still a challenge although intralesional injections of triamcinolone acetonide (TAC) are effective, they have frequently linked adverse effects. Pentoxifylline (PTX) is an anti-fibrotic and anti-inflammatory, and vasodilator. It has not yet been tested for intralesional injection in keloids. The aim of the study is to study the efficacy of intralesional pentoxifylline versus triamcinolone acetonide in keloid scars of 40 patients. In this study, 40 patients with keloid scars regardless of the cause of keloid born, 20 patients have injected with intralesional triamcinolone acetonide, and 20 patients with intralesional pentoxifylline every two weeks until the lesion flatted or a maximum 6 sessions. Evaluation of Patient response to treatment was done by utilizing the verbal rating scale and Vancouver scar scale. Between groups A& B there is no statistically significant difference in height, color, the surface of the keloid, pigmentation consistency, verbal rating scale, visual analog scale (improvement in keloid), patient satisfaction, and several sessions for best results.

Assessment of intralesional injection of botulinum toxin type A in hypertrophic scars and keloids: Clinical and pathological study.

Keloids and hypertrophic scars are cosmetic problems with significant morbidity. Many clinical modalities were tried in order to modulate the disfigurement related to these pathologic scars. To evaluate the clinical and histopathological effects of Botulinum toxin type A (BTX-A) injection on keloids and hypertrophic scars. Twelve patients with keloids and 8 with hypertrophic scars were enrolled in this study. Botulinum toxin type A was injected intralesional (1 session/month) for three sessions. Clinical outcome was assessed via Vancouver Scar Scale (VSS), Observer Scar Assessment Scale (OSAS), and the Patient Scar Assessment Scale (PSAS). Histologic grading scores were used to assess the changes in the quality of collagen and elastic tissues and image analysis was used to detect their quantitative morphometric changes. This study showed a high statistically significant difference between baseline and the result after each of the three sessions of injection and 3, 6months after the last session regarding VSS, OSAS, and PSAS with p value ≤0.001 for each. The study also showed that there was a statistically significant difference between the histopathologic findings before injection of BTX and 1month after the third session regarding all parameters used. Botulinum toxin type A can be a good therapeutic maneuver for management of keloid and hypertrophic scars with significant clinical and histologic improvement.

Needling, lasers, and Meso-Botox for hypertrophic and keloidal scars: A comprehensive review study on promising procedural treatments.

Scars are among the most prevalent referral cases of dermatology clinics, including atrophic, hypertrophic, or keloidal scars. Approach to scar usually needs a holistic trend, attention to individualized characteristics, and combination therapy. Scars usually need multiple sessions of therapy and the use of combination therapeutic approaches to reach the most acceptable outcomes by safe modalities. Studies on scars are always one of the most important fields of research in medicine, especially in dermatology. For writing this review study, we searched all the databases to find the most relevant and the newest studies related to our topic, because based on expert opinion, this topic may be really practical and interesting for dermatologists and all physicians of various specialties or subspecialties who manage and treat various kinds of scars, including hypertrophic scars and keloids. Based on our results, we concluded that different procedures, which basically use needling, lasers, especially pulsed dye laser (PDL) and carbon dioxide (CO2) laser, and MesoBotox (micro-injection of botulinum toxin), are really promising therapeutic options for hypertrophic and keloidal scars and a combination of these therapies results in more efficacy and lesser side effects in the field of scar management.

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 etal. (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.

LB1008 Prophylactic treatment of auricular keloid recurrence post excision using topical imiquimod

Introduction: Keloid scars are difficult to treat and result from aberrant wound healing and have recurrence rates of 50% to 80% without treatment. Clinicians who are comfortable with surgical removal often offer patients post excision prophylactic options such as glucocorticoid creams, pressure dressings, and radiation. However, these therapies can be timely for patients and may involve poor compliance. The exact mechanism of keloid growth is unknown, but TGF-β has been theorized to play a role in fibroblast activation.

Intralesional penicillamine in the treatment of keloids and hypertrophic scars

Background: Many therapeutic options have been tried in the treatment of keloid and hypertrophic scars, but no one is superior to others. Penicillamine has been used systemically but not tested as intralesional. Objective: The aim of this study was to evaluate the effectiveness & safety of intralesional penicillamine for treatment of keloids and hypertrophic scars. Patients and Method: this is open labeled therapeutic trial study encountered in Department of Dermatology and Venereology in Al-Yarmouk teaching Hospital, Baghdad-Iraq. Collection of data was carried out during the period between May 2010 – February 2011. This study included 28 patients with keloids and hypertrophic scars. Penicillamine was prepared as a solution for intralesional injection by dissolving (250mg) of Penicillamine (Artamin)® by SANDOZ in (10ml) distilled water in sterilized container to obtained (2.5%) concentration of Penicillamine and autoclaved at 121C0 for 20 min before use. Penicillamine was administered with 27-gauge needle syringe without anesthesia. Seventy percent ethanol was used as an antiseptic agent before injection. Four sessions of intralesional injection were given at intervals of 15 days each.