Treatment Of Keloids Research Articles

Exploration of a Predictive Model for Keloid and Potential Therapeutic Drugs Based on Immune Infiltration and Cuproptosis-Related Genes.

The aim of this study was to investigate the correlation between cuproptosis-related genes and immunoinfiltration in keloid, develop a predictive model for keloid occurrence, and explore potential therapeutic drugs. The microarray datasets (GSE7890 and GSE145725) were obtained from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between keloid and nonkeloid samples. Key genes were identified through immunoinfiltration analysis and DEGs and then analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by the identification of protein-protein interaction networks, transcription factors, and miRNAs associated with key genes. Additionally, a logistic regression analysis was performed to develop a predictive model for keloid occurrence, and potential candidate drugs for keloid treatment were identified. Three key genes (FDX1, PDHB, and DBT) were identified, showing involvement in acetyl-CoA biosynthesis, mitochondrial matrix, oxidoreductase activity, and the tricarboxylic acid cycle. Immune infiltration analysis suggested the involvement of B cells, Th1 cells, dendritic cells, T helper cells, antigen-presenting cell coinhibition, and T cell coinhibition in keloid. These genes were used to develop a logistic regression-based nomogram for predicting keloid occurrence with an area under the curve of 0.859 and good calibration. We identified 32 potential drug molecules and extracted the top 10 compounds based on their P-values, showing promise in targeting key genes and potentially effective against keloid. Our study identified some genes in keloid pathogenesis and potential therapeutic drugs. The predictive model enhances early diagnosis and management. Further research is needed to validate and explore clinical implications.

Keloid treatment assessment measures: A literature review

AbstractKeloids are an exaggerated response to cutaneous trauma that has both a physical and psychological burden for patients. Keloids have high recurrence rates and are monitored years after treatment. There is currently no widely accepted assessment measure specifically for keloids. The purpose of this review was to compare available assessment measures for keloids. Eleven assessment measures were assessed based on validity, reliability, limitations, parameters, technological influence and feasibility. Only two assessment measures (Detroit Keloid Scale and the Keloid Area and Severity Index) were specific for keloids, easy to use, had no cost and were suitable for longitudinal use. These measures, in conjunction with quality of life measures such as the Dermatology Life Quality Index, could be used to provide a detailed and longitudinal assessment of keloid treatment.

Low-Frequency Ultrasound Sensitive Piezo1 Channels Regulate Keloid-Related Characteristics of Fibroblasts.

Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo-type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low-frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient-derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF-1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx-4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient-derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.

Inhibitory effect of a novel Curcumin derivative DMC-HA on keloid fibroblasts.

Keloids pose a significant dermatological challenge, marked by abnormal fibroblast proliferation and excessive collagen deposition in response to skin injury or trauma. In the present study, we introduce DMC-HA, a derivative of Curcumin, as a promising candidate for keloid treatment. DMC-HA is poised to provide superior therapeutic benefits compared to Curcumin due to its structural modifications. Examining the comparative effects of DMC-HA and Curcumin on keloid fibroblasts can offer insights into their potential as therapeutic agents and the underlying mechanisms in keloid pathogenesis. In our study, CCK-8 experiments revealed that, at equivalent concentrations, DMC-HA demonstrated greater efficacy in inhibiting the proliferation of keloid fibroblasts compared to Curcumin. Flow cytometry analysis indicated that DMC-HA induced fibroblast apoptosis more significantly than Curcumin at the same concentration. Further data demonstrated that DMC-HA notably increased the production of reactive oxygen species (ROS), upregulated the expression levels of Bax, cleaved PARP, and cleaved Caspase-3. Interestingly, the impact of DMC-HA was reversed upon the application of the antioxidant NAC. Additionally, DMC-HA could suppress IL-6-induced increased expression of p-STAT3. Collectively, our findings suggest that DMC-HA is more effective than Curcumin in inhibiting the proliferation of keloid fibroblasts. The underlying mechanism of its action appears to be associated with the augmentation of ROS induction and the concurrent inhibition of STAT3 activation.

Application of fractional carbon dioxide laser monotherapy in keloids: A meta-analysis.

There is no evidence-based guidance on the use of fractional CO2 laser in the excision of scars. To explore the effectiveness and safety of fractional CO2 laser in the treatment of keloids. In this meta-analysis, we searched the PubMed, Embase, and Cochrane databases from inception to April 2023. We only included studies reporting fractional CO2 laser treatment of keloids. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. The pooled results showed that the Vancouver Scar Scale (VSS) parameters of height weighted mean difference (WMD) = -1.10, 95% confidence interval (CI): -1.46 to -0.74), pigmentation (WMD = -0.61, 95% CI: -1.00 to -0.21), and pliability (WMD = -0.90, 95% CI: -1.17 to -0.63) were significantly improved after fractional CO2 laser treatment of keloids. However, vascularity did not significantly change. Additionally, the total VSS was significantly improved after treatment (WMD = -4.01, 95% CI: -6.22 to -1.79). The Patient Scars Assessment Scale was significantly improved after treatment (WMD = -15.31, 95% CI: -18.31 to -12.31). Regarding safety, the incidences of hyperpigmentation, hypopigmentation, pain, telangiectasia, and atrophy were 5%, 0%, 11%, 2% (95% CI: 0%-6%), and 0% (95% CI: 0%-4%), respectively. Fractional CO2 laser is effective in the treatment of keloids and can effectively improve the height, pigmentation, and pliability of scars, and patients are satisfied with this treatment. Further studies should explore the role of combination therapy.

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.

Utility of Hyaluronidase in Combination with Triamcinolone Acetonide and 5-Fluorouracil in Treatment of Hypertrophic Scars and Keloids: A Comparative Study

Background: Keloids and hypertrophic scars are a commonly encountered problem in dermatology. There are many treatment modalities available with variable efficacy and recurrences. This study highlights the use of hyaluronidase with triamcinolone acetonide (TAC) and 5-fluorouracil (5-FU). Purpose: To assess the utility of hyaluronidase in combination with TAC and 5-FU in treatment of hypertrophic scars and keloids. Methods: In this study a combination of hyaluronidase along with TAC and 5-FU was given in one part and a combination of TAC and 5-FU was given in another half of same hypertrophic scar/keloid keeping 1cm gap in between the two untreated at 4 weekly interval for 24 weeks. Results were assessed by measuring height, volume of lesion and their percentage decrease. Also, pliability, vascularity, pigmentation of lesion and Vancouver scar assessment scale score were assessed. Side effects like ulceration, surrounding skin atrophy and telangiectasias were noted. Results: There was a reduction in all the parameters in both the treatment segments. Faster improvement in height, volume, pliability, vascularity, pigmentation, and Vancouver scar assessment scale score was noted with combination of hyaluronidase, TAC, and 5-FU compared to TAC and 5-FU alone. Side effect profile of ulceration, surrounding skin atrophy and telangiectasias was comparable in both the segments. Conclusion: Combination of hyaluronidase along with TAC and 5-FU offered a better outcome and faster response when compared to combination of TAC and 5-FU.

An Innovative Single‐Stage Approach of High‐Tension Keloid Excision and Reconstruction Using Acellular Dermal Matrix and Epidermal Skin Grafting

The treatment of keloids, particularly in high‐tension areas, is challenging due to their extension beyond the original wound boundaries and high recurrence rates, thereby rendering traditional treatments ineffective. In this study, we investigated the effectiveness of a novel single‐stage treatment approach that combined acellular dermal matrix (ADM) with keloid‐specific epidermal skin grafting. To further prevent recurrence after neo‐skin formation, the treatment was followed by fractionated laser and radiation therapy (LCR). Seven patients with high‐tension keloids, including one with keloids at two locations, were treated and followed‐up for an average of 15.9 months. The patients showed significant improvements in wound healing and skin appearance, with a marked reduction in the Patient and Observer Scar Assessment Scale (POSAS) (scores from 91.1 ± 5.6 to 23.8 ± 6.1 (p < 0.001)). This approach effectively minimizes tension, reduces the likelihood of keloid recurrence, and serves as a viable alternative to conventional methods that often involve challenges related to donor‐site acquisition. No recurrence was observed during the follow‐up period, indicating a promising innovation in the management of extensive keloids and offering improved healing and esthetic outcomes, particularly in high‐tension areas.

Artificial keloid skin models: understanding the pathophysiological mechanisms and application in therapeutic studies.

Keloid is a type of scar formed by the overexpression of extracellular matrix substances from fibroblasts following inflammation after trauma. The existing keloid treatment methods include drug injection, surgical intervention, light exposure, cryotherapy, etc. However, these methods have limitations such as recurrence, low treatment efficacy, and side effects. Consequently, studies are being conducted on the treatment of keloids from the perspective of inflammatory mechanisms. In this study, keloid models are created to understand inflammatory mechanisms and explore treatment methods to address them. While previous studies have used animal models with gene mutations, chemical treatments, and keloid tissue transplantation, there are limitations in fully reproducing the characteristics of keloids unique to humans, and ethical issues related to animal welfare pose additional challenges. Consequently, studies are underway to create in vitro artificial skin models to simulate keloid disease and apply them to the development of treatments for skin diseases. In particular, herein, scaffold technologies that implement three-dimensional (3D) full-thickness keloid models are introduced to enhance mechanical properties as well as biological properties of tissues, such as cell proliferation, differentiation, and cellular interactions. It is anticipated that applying these technologies to the production of artificial skin for keloid simulation could contribute to the development of inflammatory keloid treatment techniques in the future.

Effect of fractional CO2 laser combined with 5-Fluorouracil injection in the treatment of Hypertrophic Scars and Keloids..

Effect of fractional CO2 laser combined with 5-Fluorouracil injection in the treatment of Hypertrophic Scars and Keloids..

Surgical treatment of keloids: Total or partial resection?

Surgical treatment of keloids: Total or partial resection?

Analysis of subsets and localization of macrophages in skin lesions and peripheral blood of patients with keloids

Keloids are a type of abnormal fibrous proliferation disease of the skin, characterized by local inflammation that lacks clear pathogenesis and satisfactory treatment. The phenomenon of distinct phenotypes, including M1 and M2 macrophages, is called macrophage polarization. Recently, macrophage polarization has been suggested to play a role in keloid formation. This study aimed to evaluate the relation between macrophage polarization and keloids and identify novel effective treatments for keloids. Differentially expressed genes were identified via RNA sequencing of the skin tissue of healthy controls and patients with keloids and validated using quantitative PCR. Multiplex immunofluorescence microscopy was used to detect different phenotypes of macrophages in keloid tissues. Finally, quantitative PCR validation of differentially expressed genes and flow cytometry were used to analyze macrophages in the peripheral blood of healthy controls and patients with keloids. Total and M2 macrophages were significantly increased in the local skin tissue and peripheral blood of patients with keloids compared with healthy controls. In addition, inflammation- and macrophage polarization-related differentially expressed genes in keloid tissue showed similar expression patterns in the peripheral blood. This study highlighted an increased frequency of total macrophages and M2 polarization in the local skin tissue and peripheral blood of patients with keloids. This systematic macrophage polarization tendency also indicates a potential genetic predisposition to keloids. These findings suggest the possibility of developing new diagnostic and therapeutic indicators for keloids focusing on macrophages.

Comparative Efficacy of Drug Interventions for Keloids: A Network Meta-analysis.

Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological problems. The optimal treatment for keloids is yet to be standardized. Intralesional injection, which is simple and nontraumatic, is one of the most commonly used treatment modalities for these lesions. In this study, we compared 5 different drugs (intralesional injections) for the treatment of keloids in terms of efficacy. We systemically searched relevant studies on PubMed, EMBASE, and Cochrane Library. Randomized clinical trials on the safety and efficacy of triamcinolone acetonide (TAC), 5-fluorouracil (5-FU), botulinum toxin A (BTA), verapamil, and bleomycin were included in this study. This network meta-analysis included a total of 1114 patients from 20 randomized controlled trials. Botulinum toxin A alone and TAC plus 5-FU exhibited significantly better efficacy than did 5-FU, TAC, and verapamil. No significant difference in efficacy between BTA alone and TAC combined with 5-FU was observed. No significant differences were noted in the adverse event rate between BTA, TAC plus 5-FU, 5-FU, and TAC. Furthermore, we performed surface under the cumulative ranking curve analyses to predict the rank of each intervention (by efficacy and adverse event rate). The predicted ranking by efficacy was as follows: TAC plus 5-FU, BTA, bleomycin, TAC, 5-FU, and verapamil; the predicted ranking by adverse events was as follows: TAC, 5-FU, TAC plus 5-FU, and BTA. Funnel plot analysis revealed no publication bias. Botulinum toxin A and TAC plus 5-FU appear to have outstanding therapeutic efficacy for keloids. The rate of adverse events was similar among BTA, TAC, 5-FU, and TAC plus 5-FU. Nonetheless, additional reviews of rigorous, large-scale randomized controlled trials are warranted for further validation of our findings.

Twist-related protein 1 promotes transforming growth factor β receptor 1 in keloid fibroblasts via regulating the stability of myocyte enhancer factor 2A.

Keloid scarring is caused by a fibroproliferative disorder due to abnormal activation of genes, the underlying mechanism of which is still unclear. The basic helix-loop-helix transcription factor Twist-related protein 1 (TWIST1) controls cell proliferation and differentiation in tissue development and disease processes. In this study, we aimed to clarify the essential role of TWIST1 in the pathogenesis of keloids. Immunohistochemistry, cell counting kit-8 assays, western blotting, PCR, matrigel invasion assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of TWIST1 in fibroblasts derived from normal skin and keloids. Mass spectrometry, ubiquitination assays, chromatin immunoprecipitation and dual luciferase reporter assay were applied to explore the interaction of TWIST1 with downstream molecules. In the present study, we confirmed that TWIST1 was upregulated in keloid tissue of patients and in keloid-derived fibroblasts (KFBs). In vitro, TWIST1 inhibition prevented KFB proliferation, invasion and activation. We also discovered a link between TWIST1 and the transforming growth factor β (TGF-β) signaling related molecules TGF-β receptor 1 (TΒR1), SMAD family member 2 (Smad2) and Smad3, and the fibrosis markers α-smooth muscle actin, collagen type I and collagen type III in KFBs. Mechanistically, we uncovered a brand-new mechanism by which TWIST1 interacts with myocyte enhancer factor 2A (MEF2A) and suppresses its ubiquitination and degradation. Using chromatin immunoprecipitation and dual-luciferase reporter assay, TΒR1 was identified as a novel downstream target of MEF2A, which directly binds to its promoter. Overexpression of TWIST1 promoted the recruitment of MEF2A to the TΒR1 promoter and restored TΒR1 functional expression. Our research highlights a significant function of TWIST1 in the development of keloid and its related fibroblasts, partially facilitated by elevated MEF2A-dependent TΒR1 expression. Blocking the expression of TWIST1 in KFBs could potentially pave a novel therapeutic avenue for keloid treatment.

Effects of Stem Cell Therapy on Keloid Treatment: A Literature Review

Fibroblasts that produce excess collagen and growth factors play a role in the pathogenesis of keloid formation. In general, keloids are treated with intralesional corticosteroids alone or with a combination of other modalities, but the recurrence rate is still relatively high, so alternative treatments such as stem cells are being investigated, one of which is Mesenchymal Stem Cells (MSC), which have proven to be useful in healing keloids. Therefore, this literature review aims to discuss the effects of stem cell therapy in the treatment of keloids. In this literature review, 36 journals were used that discussed stem cell therapy in the treatment of keloids taken from various journal sources, namely Google Scholar, Pubmed, Medline, Ebsco, Hindawi, and Cochrane which were published within the last 10 years. According to the source, MSC is divided into 2 types, namely Adipose Mesenchymal Stem Cells (AMSC) and Bone Marrow Mesenchymal Stem Cells (BMMSC). In several studies, AMSC is known to reduce the expression of TGF-β1, COL-1, and COL-2 proteins, and has been shown to inhibit the proliferation of fibroblasts in keloid patients. Whereas in the BMMSC study that was applied with Hydroxybutyl chitosan (HBC) and Arg-Gly-Asp (RGD) hydrogels for 7 days, it was shown to significantly reduce nodular collagen fibers (p<0.05). Keloids occur due to excessive production of collagen and are influenced by various factors such as age, gender, skin color, and genetics. Stem cell therapy, such as MSC, has been proven in various studies to be an alternative treatment for keloids

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.

The Combined Application of Bleomycin and Triamcinolone for Treating Refractory Keloids.

Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined. The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids. In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded. In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%). The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies.

Efficacy of surgical resection and ultra-reduced tension suture combined with superficial radiation in keloid treatment.

There are many available treatment options for keloid; however, single treatments are usually less effective. Therefore, more scientifically rational and effective combined treatment methods should be sought to solve the pain associated with keloids. To explore the efficacy and safety of surgical resection and ultra-reduced tension suture combined with superficial radiation as keloid treatment. Fifteen keloid patients admitted to Qingdao Eighth People's Hospital from June 2020 to January 2022 were enrolled in this retrospective analysis. All patients underwent a comprehensive treatment approach comprising surgical resection, ultra-reduced tension suture incision, and superficial radiation therapy within 24 h postoperatively. The modified Vancouver Scar Scale (mVSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to evaluate the treatment effect, whereas the efficacy, adverse effects, and recurrence rate were observed according to the 12-mo follow-up after treatment. The mVSS and POSAS scores at 1 and 6 mo after combination treatment decreased compared to before treatment (P < 0.001), and the overall response rate was 93.3%. Only one case recurred, yielding a 6.7% recurrence rate. The incidence of local chromour sedimentation rate in 1-3 mo after radiotherapy was 33.3% (5 patients), all subsiding after 6-9 mo, without complications, such as delayed wound healing or dermatitis. Surgical resection, super subtraction sutures, and superficial radiotherapy are treatment methods with short courses, low recurrence rates, and good safety profiles.

Liposomes and transferosomes in the delivery of papain for the treatment of keloids and hypertrophic scars

Hypertrophic scars and keloids are characterized by an excessive collagen deposition. The available treatment options are invasive and can result in recurrence of scar formation. Using liposomes and transferosomes for the topical delivery of papain, a proteolytic enzyme, can be effective treatment. The objective of the study is to formulate papain-loaded liposomes and transferosomes, characterize the formulations, and study in vitro permeation using shed snake skin and Sprague-Dawley rat skin as models for stratum corneum and full thickness skin. Papain-loaded liposomes and transferosomes were formulated using the thin-film hydration method for the delivery of papain across the stratum corneum barrier. An in vitro permeation study carried out using shed-snake skin and Sprague-Dawley rat skin models showed that transferosomes were able to deliver papain across the stratum corneum barrier, while papain solution and papain liposomes were not able to cross the barrier. However, transferosomes were not able to deliver papain across the full thickness rat skin model suggesting the deposition of papain loaded transferosomes in the epidermal or dermal layer of skin. In addition, an ex-vivo model was used to analyze the effect of papain exposure on the morphology of the epidermis taken from rat skin exposed to papain solution, papain in transferosomes and papain in liposomes. Papain in solution resulted in a noticeable degradation of the epidermis, but when embedded in either transferosomes or liposomes there was no noticeable change when compared to control animals. The cytotoxicity study performed using HeLa cells showed that the cells were viable at papain concentrations lower than 0.01 mg/ml.

Needle-Free Jet Injector-Assisted Triamcinolone Treatment of Keloids and Hypertrophic Scars is Effective and Well Tolerated in Children.

Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia. We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars. A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction. Six female patients and five male patients aged 5-17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were 'satisfied' and five patients were 'very satisfied' with the treatment. Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.