Keloid Research Articles

A systematic review of the efficacy, safety and satisfaction of regenerative medicine treatments, including platelet-rich plasma, stromal vascular fraction and stem cell-conditioned medium for hypertrophic scars and keloids.

The primary objective of this study is to examine the efficiency of various regenerative medicine approaches, such as platelet-rich plasma, cell therapy, stromal vascular fraction, exosomes and stem cell-conditioned medium, in the process of healing hypertrophic and keloid scars. Major databases including PubMed, Scopus and Web of Science were systematically searched, and based on the content of the articles and the inclusion and exclusion criteria, eight articles were selected. Out of these eight articles, there were two non-randomized clinical trial studies (25%), one randomized, single-blinded comparative study (12.5%), one retrospective clinical observational study (12.5%) and four randomized clinical trial studies (50%). We employed EndNote X8 and Google Sheets to conduct article reviews and extract relevant data. Following the review phase, the studies underwent analysis and categorization. In all eight reviewed studies, the effectiveness of regenerative medicine in treating hypertrophic scars and keloids has been proven. Out of these studies, five (62.5%) focused on the effectiveness of platelet-rich plasma, two study (25%) examined the effectiveness of stromal vascular fraction and one study (12.5%) explored the efficacy of stem cell-conditioned medium. In two studies (25%), the treatment methods were added to standard treatment, while in six studies (75%), regenerative medicine was used as the sole treatment method and compared with standard treatment. The use of these treatment methods did not result in any serious side effects for the patients. Regenerative medicine is an effective method with minimal side effects for the treatment of hypertrophic scars and keloids. It can be used as a monotherapy or in combination with other treatment methods. However, further studies are needed to thoroughly evaluate the effectiveness of all sub-branches of this method.

Kyselina hyaluronová – význam a možnosti využití v otorinolaryngologii

kyselina hyaluronová – otorinolaryngologie – léčba Summary Hyaluronic acid (HA) is a linear, naturally occurring polysaccharide of high molecular weight. It is part of a number of bio logical processes, especially regulatory, anti-inflammatory, immunosuppressive or antiproliferative. It significantly binds water and participates in the maintenance of tissue viscoelasticity, in the supramolecular spatial arrangement of proteoglycans in the extracellular matrix and in the regulation of osmotic pressure, which significantly affects tissue homogeneity and its homeostatic integrity. Due to these properties, non-immunogenic HA can be used in many clinical applications. In otorhinolaryngology, the possibilities of its use are wide, especially in otology, laryngology, rhinology or in the treatment of inflammatory conditions and keloid scars. Some potential areas of use are still in the experimental stage (gene therapy). Key words hyaluronic acid – otorhinolaryngology – treatment

RNA-seq unravels distinct expression profiles of keloids and Dupuytren's disease

Keloid scars and Dupuytren's disease are two common, chronic, and incurable fibroproliferative disorders that, among other shared clinical features, may induce joint contractures. We employed bulk RNA sequencing to discern potential shared gene expression patterns and underlying pathological pathways between these two conditions. Our aim was to uncover potential molecular targets that could pave the way for novel therapeutic strategies. Differentially expressed genes (DEGs) were functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein-interaction (PPI) networks were constructed by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Molecular Complex Detection (MCODE) plugin was used for downstream analysis of the PPI networks. A total of 1922 DEGs were identified within Dupuytren's and keloid samples, yet no overlapping gene expression profiles were detected. Significantly enriched GO terms were related to skin development and tendon formation in keloid scars and Dupuytren's disease, respectively. The PPI network analysis revealed 10 genes and the module analysis provided six protein networks, which might play an integral part in disease development. These genes, including CDH1, ERBB2, CASP3 and RPS27A, may serve as new targets for future research to develop biomarkers and/or therapeutic agents.

Microneedle Electroporation for Intralesional Administration of Corticosteroid Treatment of Keloid Scar.

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Keloids are transcriptionally distinct from normal and hypertrophic scars.

Wound healing and skin regeneration after injury are complex biological processes, and deep injuries with a high degree of tissue destruction may result in severe scar formation. Clinically, scars can be classified into normal, hypertrophic and keloid scars. However, the molecular signature of each scar type is currently not known. The aim of this study was to reveal the transcriptional landscape of normal, hypertrophic and keloid skin scars following hand and plastic surgery based on total RNA sequencing. Eighteen skin scar samples from hand and plastic surgeries of human donors were minced directly after removal and stored in TRIzol (Thermo Fisher, USA). Samples were then subjected to RNA isolation, cDNA library preparation, bulk RNA sequencing and bioinformatics analysis. We show that keloid scars transcriptionally differed from normal and hypertrophic scars. Normal and hypertrophic scars presented overlapping clustering, and eight genes were shown to be commonly expressed between hypertrophic and normal scars. No genes were specifically expressed at a higher level in keloid and normal scars. Based on gene ontology pathway analysis, genes with a higher level of expression in keloid scars lead to increased (extra-) cellular matrix proliferation and cell interaction. Moreover, tumour-like genes were more highly expressed in keloid scars, supporting the clinical impression of strong and diffuse growth. This study furthers our understanding of the classification of differential scar types based on molecular signature, which may shed light on new diagnostic and therapeutic strategies for keloid scars in the future.

Screening and identification of hub genes of scar physique via weighted gene co-expression network analysis.

Scar physique refers to the abnormal repair of skin injury in some people, which may easily lead to keloid or hypertrophic scar. However, the mechanism of scar physique is still unclear. GSE108110 was obtained from the gene expression omnibus database. Differently expression genes (DEGs) between normal skin tissue of non-scar physique individuals and normal skin tissue of scar physique individuals were screened by R package "limma". Weighted gene co-expression network analysis was performed to find highly relevant gene modules. Functional annotation of DEGs was made. Protein-protein interaction network was constructed, and the identification and analysis of hub DEGs were performed, including identification of hub DEGs associated with scar diseases, MiRNA of hub DEGs prediction, and functional annotation of miRNA. A total of 1389 up-regulate DEGs and 1672 down-regulate DEGs were screened. weighted gene co-expression network analysis analysis showed that the dendrogram and heatmap were used to quantify module similarity by correlation. The associations between clinic traits and the modules were identified based on the correlation between module and scar physique. Eight common hub genes were obtained. The comparative toxicogenomics database shows common hub genes associated with scar tissue. Gene ontology and Kyoto encyclopedia of genes and genomes analysis were significantly enriched in "fibroblast growth factor receptor signaling pathway", "epidermal growth factor receptor signaling pathway", "G1/S transition of mitotic cell cycle", protein polyubiquitination", and others. The 8 hub genes might be involved in the development of scarring and used as early diagnosis, prevention and treatment of scar physique.

Needle-free electronically-controlled jet injector treatment with bleomycin and lidocaine is effective and well-tolerated in patients with recalcitrant keloids.

The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.

Needle-free electronically controlled jet injection with corticosteroids in recalcitrant keloid scars: a retrospective study and patient survey

First-line treatment of keloids consists of intralesional needle injections with corticosteroids, but generally entails multiple painful sessions, resulting in variable clinical outcomes. Novel needle-free jet injectors may facilitate more effective and patient-friendly dermal drug delivery. Here, we evaluated the effectiveness, tolerability and patient satisfaction of intralesional triamcinolone-acetonide (TCA) treatment in recalcitrant keloids using an electronically controlled pneumatic injector (EPI). A retrospective study was conducted in recalcitrant keloid patients with a history of severe pain during needle injections who received three sessions of EPI + TCA. Outcome measures included Patient and Observer Scar Assessment Scale (POSAS), Global Aesthetic Improvement Scale (GAIS), treatment-related pain (NRS), adverse effects, and patient satisfaction (survey). Ten patients with in total 283 keloids were included. The POSAS score significantly improved at follow-up and GAIS was reported as ‘(very) improved’ for all patients. EPI + TCA was well-tolerated with a significantly lower NRS pain score compared to needle + TCA (pilot treatment). Only minor adverse effects occurred, and 90% of patients preferred EPI over needle treatment. EPI + TCA is an effective and tolerable treatment for patients with recalcitrant keloids. The minimal treatment-related pain and high patient satisfaction makes it a promising treatment for patients with needle-phobia and/or severe pain during needle injections.

Clinical Features and the Outcome Evaluations of Keloid and Hypertrophic Scar Treatment with Triamcinolone Injection in Mekong Delta, Vietnam - A Cross-Sectional Study.

Excessive scarring is a common problem that can have significant cosmetic and psychological consequences for patients. Intralesional injection therapy, such as the use of triamcinolone, has emerged as an effective treatment option for hypertrophic scars. The objective of this study was to describe the morphological features of hypertrophic scars, categorize them, and evaluate the efficacy of triamcinolone injection therapy in treating these scars. A cross-sectional descriptive study of 80 patients with hypertrophic scars treated with triamcinolone intralesional injection at Can Tho University of Medicine and Pharmacy Hospital from 5/2018 to 5/2021. There were 80 patients in all, with a male/female ratio of 1/1.05 and a median age of 15-35. There were 129 scars in all, with scar age >1 year accounting for 83%, keloid scars accounting for 64%, and hypertrophic scars accounting for the remaining 36%. Scars are most commonly seen on the trunk, accounting for 53.5% of all scars, particularly on the anterior chest wall. When the source of scars was discovered, trauma and acne accounted for 24% and 23%, respectively, while the rest were predominantly spontaneous scars, accounting for 49%. Scarring and discomfort of mild to moderate severity were common clinical symptoms; scars larger than 5cm in size had more symptoms than scars smaller than 5cm. Prior to the therapy, the mean Vancouver Score Scale-VSS was 6.55±2.13. After 24 weeks of the therapy, 96.7% of patients had entirely improved itching symptoms, 75% had completely improved pain, and 25% still had minimal pain. After therapy, the mean Vancouver Score Scale-VSS was 2.55±1.81 (p<0.05). At week 24, 3.75% of patients experienced skin shrinkage, 3.75% experienced depigmentation, and 13.75% experienced vasodilation. Triamcinolone intralesional injection should be utilized as a first-line therapy for hypertrophic scarring.

114 Identifying the mechanism of tension-associated tissue fibrosis based on integrative single cell RNA sequencing analysis on keloid scar

114 Identifying the mechanism of tension-associated tissue fibrosis based on integrative single cell RNA sequencing analysis on keloid scar

Modelling Keloids Dynamics: A Brief Review and New Mathematical Perspectives.

Keloids are fibroproliferative disorders described by excessive growth of fibrotic tissue, which also invades adjacent areas (beyond the original wound borders). Since these disorders are specific to humans (no other animal species naturally develop keloid-like tissue), experimental in vivo/in vitro research has not led to significant advances in this field. One possible approach could be to combine in vitro human models with calibrated in silico mathematical approaches (i.e., models and simulations) to generate new testable biological hypotheses related to biological mechanisms and improved treatments. Because these combined approaches do not really exist for keloid disorders, in this brief review we start by summarising the biology of these disorders, then present various types of mathematical and computational approaches used for related disorders (i.e., wound healing and solid tumours), followed by a discussion of the very few mathematical and computational models published so far to study various inflammatory and mechanical aspects of keloids. We conclude this review by discussing some open problems and mathematical opportunities offered in the context of keloid disorders by such combined in vitro/in silico approaches, and the need for multi-disciplinary research to enable clinical progress.

Managing Surgical Site Scarring as a Complication of Permanent Pacemaker Implantation

ABSTRACT Pathologic collagen deposition in the form of keloid or hypertrophic scarring can result from any procedure that involves skin barrier disturbance. In this case report, we present a case of a patient who developed hypertrophic scarring complicated by the uncommon symptom of dysesthesia after pacemaker implantation and was successfully treated with intralesional corticosteroids. Although intralesional steroid injection is a well-known treatment option for hypertrophic scarring, both the rarity of hypertrophic scarring after pacemaker implantation and the seriousness of the complications that can result from pocket seeding and infection after injection at a pacemaker site are noteworthy. This case thus serves as a precautionary guideline for providers who will encounter similar cases.

Evaluations of patient-specific bolus fabricated by mold-and-cast method using computer numerical control machine tools†.

The patient-specific bolus fabricated by a mold-and-cast method using a 3D printer (3DP) and silicon rubber has been adopted in clinical practices. Manufacturing a mold using 3DP, however, can cause time delays due to failures during the 3D printing process. Thereby, we investigated an alternative method of the mold fabrication using computer numerical control (CNC) machine tools. Treatment plans were conducted concerning a keloid scar formed on the ear and nose. The bolus structures were determined in a treatment planning system (TPS), and the molds were fabricated using the same structure file but with 3DP and CNC independently. Boluses were then manufactured using each mold with silicone rubbers. We compared the geometrical difference between the boluses and the planned structure using computed tomography (CT) images of the boluses. In addition, dosimetric differences between the two measurements using each bolus and the differences between the measured and calculated dose from TPS were evaluated using an anthropomorphic head phantom. Geometrically, the CT images of the boluses fabricated by the 3DP mold and the CNC mold showed differences compared to the planned structure within 2.6mm of Hausdorff distance. The relative dose difference between the measurements using either bolus was within 2.3%. In conclusion, the bolus made by the CNC mold benefits from a stable fabricating process, retaining the performance of the bolus made by the 3DP mold.

Management of Keloid Scars with Radiotherapy

Keloid scars are a challenging dermatological condition characterized by excessive scar tissue formation beyond the boundaries of the original wound. This review explores the epidemiology and clinical significance of keloid scars, emphasizing the substantial impact they have on patients' quality of life and psychosocial well-being. The theoretical framework delves into the definition of keloid scars, identifies risk factors contributing to their development, discusses potential complications, and outlines current management strategies. The discussion section evaluates the role of radiotherapy in managing keloid scars, providing insights into its mechanisms of action, efficacy, and safety. The conclusion emphasizes the importance of a personalized approach to keloid scar management, with radiotherapy as a valuable therapeutic option.

Skin care for scars: Where we have been and what's new

AbstractBackgroundThe process of scar formation and wound healing is an important topic as different skin types can heal diversely. Scars of all ranges, from fine line scars that are barely a bother to hypertrophic and keloid scars accompanied by bothersome symptoms, have been trouble to treat with many diverse products and hypotheses historically. The diverse appearance of scars is astounding with colors, shapes, sizes, and symptoms, including pain and pruritis, affecting patients differently.MethodsThis paper will dive into the diverse treatments of scar therapy and different published studies done to prove efficacy, along with different scar subtypes.ResultsTreatments mentioned are topical and consist of silicone‐based products, as well as non‐silicone‐based products, like onion extract, green tea, Aloe vera, hydrocolloid dressings, vitamin A derivatives, vitamin E, vitamin D, moist exposed burn ointment, imiquimod, and mitomycin.ConclusionIn sum, wound healing is a difficult process and patient outcomes vary depending on skin and scar types, thus scar therapies should continue to be studied before concluding the best skin care for scars.

Modern view on the problem of keloid scars

Modern view on the problem of keloid scars

Metformin ointment may relieve hypertrophic and keloid scars.

Metformin ointment may relieve hypertrophic and keloid scars.

Ubiquitin-specific peptidase 11 promotes development of keloid derived fibroblasts by de-ubiquitinating TGF-β receptorII

BackgroundKeloid scars occur as a result of abnormal wound healing caused by trauma or inflammation of the skin. The progression of keloids is dependent on genetic and environmental influences. The incidence is more prevalent in people with darker skin tones (African, Asian and Hispanic origin). Studies have demonstrated that transforming growth factor (TGF) β/Smad signalling has an essential function in keloid as well as that USP11 could modulate the activation of TGFβ/Smad signalling and impact the progression of the fibrotic disease. Nonetheless, the potential mechanisms of USP11 in keloid were still unclear. The authors postulated that USP11 up-regulates and augments the ability of proliferation, invasion, migration and collagen deposition of keloid-derived fibroblasts (KFBs) through deubiquitinating TGF-β receptor II (TβRII). MethodsFibroblast cells were isolated from keloid scars in vitro. Lentivirus infection was utilized to knockdown and over-express the USP11 in KFBs. Influence of USP11 on proliferation, invasion and migration of KFBs, and expression level of TβRII, Smad2, Smad3, α-SMA, collagen1 and collagen3 were assayed by CCK8, scratching, transwell, Western blot and real-time quantitative polymerase chain reaction. The interactions between USP11 and TβRII were examined using ubiquitination assays and co-immunoprecipitation. To further confirm the role of USP11 in keloid growth, we performed animal experiments. ResultsResults show that down-regulated USP11 markedly suppressed the ability of proliferation, invasion and migration of keloid derived-fibroblasts in vitro and reduce the expression of TβRII, Smad2, Smad3, αSMA, collagen1 and collagen3. In addition, over-expression of USP11 demonstrated the contrary tendency. Ubiquitination experiments and co-immunoprecipitation demonstrated that USP11 was interacting with TβRII and deubiquitinated TβRII. Interferences with USP11 inhibited growth of keloid in vivo. Additionally, we have verified that knockdown of USP11 has no significant effect on normal skin fibroblasts. ConclusionUSP11 elevates the ability of proliferation, collagen deposition, invasion and migration of keloid–derived fibroblasts by deubiquitinating TβRII.

Pruritus in keloid scars: mechanisms and treatments.

Keloids occur after cutaneous injury and can cause distress due to physical appearance and associated symptoms such as pain and pruritus. Keloid-associated pruritus is a common manifestation and has negative impacts on quality of life. The mechanism underlying this type of pruritus is multifactorial and thought to involve small nerve fiber damage, neurogenic inflammation, and a Th2-predominant inflammatory response. Various agents have been shown to reduce keloid pruritus, including intralesional corticosteroids, botulinum toxin A, 5-fluorouracil, and bleomycin. Other treatment modalities such as cryotherapy and hyperbaric oxygen therapy are also effective. Future treatments targeting the mechanisms involved in keloid-associated itch could provide improvements in pruritus and quality of life in these patients, but further studies on the efficacy of these agents are needed.

Comparison of the efficacy and safety of intralesional triamcinolone injection with the combination of triamcinolone, five fluorouracil, and hyluronidase enzyme in the treatment of keloids and hypertrophic scars

Hypertrophic and keloids scars are frequent benign disorders. These disorders occur due to the deposition of aberrant collagen in the scar tissue and can cause significant clinical presentations such as itching, discomfort, and disfigurement. Many therapeutic approaches have been proposed for their treatment without any acceptable outcomes. Methods After receiving ethical committee approval, a randomized prospective control trial was done in the clinic of plastic surgery at Suez Canal University Hospital for 3 months, from June 2023 to September 2023. 30 patients of both sexes and above the age of 14 were enrolled in the study and classified into two equal groups of 15 each: group (A) patients injected with triamcinolone alone, and group (B) patients injected with the combined therapy. All lesions were evaluated at 4, 8, and 12 weeks of injection. Scars were evaluated by the patient and observer scar assessment scale (POSAS) score. Complications such as atrophy of the skin, superficial ulcers, and telangiectasia have also been reported during or after injection. Results At 12 weeks of injection, both doctors and patients gave remarkably lower patient and observer scar assessment scale scores compared with those before injection, and there was a statistically significant difference between both groups. Group (B) scars improved more than group (A) scars in terms of itching, discomfort, pain, movement limitation, and aesthetic concern. Recurrence occurred only in group (A) patients. Conclusion The injection of the combined solution is effective more than triamcinolone alone. It results in a faster response, and an acceptable aesthetic outcome with few adverse effects.