Scar outcomes for conservatively managed children post burn injury: A retrospective study.

Hypertrophic scarring is a significant complication post burn injury, especially for delayed healing after 3 weeks. Burn injuries healing prior to 3 weeks also have the potential to develop hypertrophic scarring, even when prescribed prophylactic conservative scar interventions. A retrospective chart audit reviewed 326 burn patients treated at a paediatric tertiary hospital from 2014 to 2019 who sustained a partial thickness burn, healed >14 days and did not receive skin grafting. A scar was deemed hypertrophic if >1 mm in height. Early hypertrophic scar prevalence was defined as 3-6 months post burn, while persistent hypertrophic scarring was defined as 12-18 months post burn. Median days to wound closure was 18. The prevalence of early and persistent hypertrophic scarring was 56.1% and 16.3%, respectively. Seventeen (5.2%) children underwent medical interventions for scar modulation. Early signs of hypertrophic scarring were seen in just over half the patients presenting to burn therapy and despite scar intervention, persistent hypertrophic scarring was seen in 16.3%. At both time points, just over half of the children presenting healed between 14 and 21 days. Therefore, children healing prior to 21 days have potential to develop hypertrophic scarring.

A Nude Mouse Model of Xenografted Hypertrophic Scar Cells to Test Therapeutics in the Skin.

BACKGROUND: Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss in vivo. METHODS: Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes TYR, TYRP1, and DCT. RESULTS: The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm vs. 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of TYR, TYRP1, and DCT compared to untreated controls (TYR: 2.7 ± 1.1 vs. 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 vs. 0.3 ± 0.7; DCT 0.7 ± 0.9 vs. 0.3 ± 1-fold change from control; n = 3). CONCLUSIONS: The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH in vivo.

The potential of RNA therapeutics in dermatology.

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.

Update on Hypertrophic Scar Management in Burn Patients.

Hypertrophic scars arise from burn injuries because of persistent inflammation in the reticular dermis. Several risk factors promote this chronic inflammation. One is tension on the burn wound/scar due to surrounding skin tightness and bodily movements. High estrogen levels and hypertension are also important systemic risk factors. Thus, to prevent burn wounds from developing into hypertrophic scars, it is important to focus on quickly resolving the reticular dermal inflammation. If conservative treatments are not effective and the hypertrophic scar transitions to scar contracture, surgical methods such as Z-plasty, full-thickness skin grafting, and local flaps are often used.

Insights into the role of adipose-derived stem cells and secretome: potential biology and clinical applications in hypertrophic scarring.

Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.

Advances in laser therapies for the scar. / ç˜¢ç—•çš„æ¿€å ‰æ²»ç–—è¿›å±•.

Scars are classified into 5 types: Superficial scars, hypertrophic scars, atrophic scars, depressed scars, and keloid. These types are primarily characterized by abnormal production of fibroblasts and collagen, as well as the disorderly arrangement of connective tissue. Laser treatment for scars involves the coordinated activation of various signaling pathways and cytokines. However, the exact pathological mechanism for scar formation remains unclear, leading to a lack of radical treatment. Recently, laser treatment has gained popularity as a new minimally invasive approach for scar treatment. The emergence of new theories such as fractional, picosecond laser, and laser-assisted drug delivery has led to continuous advance in laser treatment. Up to now, it has been developed numerous novel treatments, including combined with drug, physical, and other treatments, which have shown superior therapeutic effects. In order to optimize laser treatment in the future, it is crucial to combine new materials with postoperative care. This will help clinicians develop more comprehensive treatment strategies. Therefore, it is important to explore treatment options that have broader applicability.

Pharmacotherapy for Keloids and Hypertrophic Scars.

Keloids (KD) and hypertrophic scars (HTS), which are quite raised and pigmented and have increased vascularization and cellularity, are formed due to the impaired healing process of cutaneous injuries in some individuals having family history and genetic factors. These scars decrease the quality of life (QOL) of patients greatly, due to the pain, itching, contracture, cosmetic problems, and so on, depending on the location of the scars. Treatment/prevention that will satisfy patients' QOL is still under development. In this article, we review pharmacotherapy for treating KD and HTS, including the prevention of postsurgical recurrence (especially KD). Pharmacotherapy involves monotherapy using a single drug and combination pharmacotherapy using multiple drugs, where drugs are administered orally, topically and/or through intralesional injection. In addition, pharmacotherapy for KD/HTS is sometimes combined with surgical excision and/or with physical therapy such as cryotherapy, laser therapy, radiotherapy including brachytherapy, and silicone gel/sheeting. The results regarding the clinical effectiveness of each mono-pharmacotherapy for KD/HTS are not always consistent but rather scattered among researchers. Multimodal combination pharmacotherapy that targets multiple sites simultaneously is more effective than mono-pharmacotherapy. The literature was searched using PubMed, Google Scholar, and Online search engines.

The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Keloid and Hypertrophic Scars Treatment.

BACKGROUND: Hypertrophic scars are contained within the site of injury and may regress over time, while keloids spread beyond the borders of the initial injury and do not regress. On histologic examination, hypertrophic scars tend to have collagen in a wavy, regular pattern, whereas keloids have no distinct pattern of collagen. OBJECTIVE: To retrospectively analyze improvement in keloid and hypertrophic scars characteristics following treatment with Ablative 10600 nm and a non-Ablative 1570 nm Hybrid Laser Device. METHODS: Treatment parameters with the ProScan Hybrid Mode were 40 W/1.3-1.5 ms for the CO2 and 12 W/4 ms for the 1570 nm in a 1:1 ratio. Outcomes were assessed based on physician scar grading as measured by the Vancouver Scar Scale and patient-reported satisfaction. Excel was used for data analysis, and a p value < 0.05 was considered statistically significant. Adverse events and patient pain were also recorded. RESULTS: A total of 31 hypertrophic scars and 30 keloid scars were treated. There was a significant reduction in Vancouver Scar Scale scores for both hypertrophic and keloid scars (62% ± 8% and 58% ± 7%; p = 2.6E-17 and p = 8.29E-26, respectively). In a scar-based comparison, a statistically significant difference was observed for all measures reflecting favorable outcomes for hypertrophic scars (VSS, p = 1.1E-05; satisfaction, p = 0.0112; pain, p = 0.00081). Only one adverse event was reported, a superficial burn treated with topical antibiotics. CONCLUSIONS: The device was found to be safe and effective, with promising results for the treatment of hypertrophic and keloid scars. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Presentation, Management, and Outcomes of Pathologic Scars Within a Pediatric Otolaryngology Practice.

OBJECTIVES: This study aims to review the spectrum of scarring that may present to an urban, pediatric otolaryngology practice and determine if associations exist between race, scar location, treatment modality, and outcomes following interventions for scarring. METHODS: Retrospective cohort study among 115 pediatric patients with 138 unique keloids or hypertrophic scars (HTS), and 141 children presenting for tonsillectomy at Tufts Medical Center. Age at presentation and sex assigned at birth were collected for both populations. For those presenting for pathologic scars, income quintile, self-identified race/ethnicity, anatomical location, treatment number and type, and clinical outcome were also analyzed. Multivariate analyses calculated adjusted odds ratios (aORs) and 95% confidence intervals to assess associations between scar subsite, intervention type, and persistence after treatment. RESULTS: Compared to individuals presenting for tonsillectomy, a disproportionate percentage of patients presenting for scarring identified as Black (26.6% vs. 13.5%) or Asian (17.4% vs. 7.1%, p = 0.016) or were male (61.7% vs. 49.7%, p = 0.053). Individuals identifying as Black or Asian were more likely to present with ear lobe and neck scars, respectively (50.0% vs. 45.5%, p = <0.001). Ear scars were significantly more likely to receive excision at initial treatment (aOR = 5.86 [1.43-23.96]) compared to other subsites, and were more likely to require >1 treatment (aOR = 5.91 [1.53-22.75]). CONCLUSION: Among pediatric patients presenting with keloids or HTS, children who identified as Black or Asian were more likely to present with ear and neck scars, respectively. Ear scars were frequently treated with excision and appear more likely to require adjuvant treatments and multiple interventions. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3127-3135, 2024.

Laser-Assisted Drug Delivery in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review.

Hypertrophic scars and keloids are the results of an exaggerated healing process and are often associated with significant patient morbidity. Fractional ablative lasers create microchannels in the skin and penetrate into the substance of the scar, inducing a normal healing response in zones of created damage. Focal delivery of scar-modulating agents into the scar through these microchannels-a process termed laser-assisted drug delivery (LADD)-is a promising and developing treatment modality. In this systematic review, we aim to critically examine the evidence of LADD in the treatment of hypertrophic scars and keloids. The evidence suggests that LADD improves outcomes in hypertrophic scars and keloids. LADD is a more effective treatment modality than the topical application of agents in hypertrophic scars and equally effective as the intralesional injection of agents in keloids. There were few reports of adverse events. Evidence supports the use of LADD as an adjunct to non-surgical measures or a treatment modality to be used before more invasive measures such as surgical excision. However, the quality of evidence supporting this conclusion is inconsistent and lacks power. Additional studies are required to optimize dosages, laser settings, and agent choices for the treatment of these lesions.

Microneedling in the Treatment of Post-burn Hypertrophic Scars.

INTRODUCTION: Post-burn hypertrophic scars are an important cause of physical discomfort, limitation of movements, psychological disorders, low self-esteem and reduced quality of life. Treatment for this condition is complex and involves several options. Microneedling, also known as minimally invasive percutaneous collagen induction, is an affordable minimally invasive option that can be combined with other treatments, including ablative ones. OBJECTIVE: The goal of this study was to present our microneedling approach for the treatment of hypertrophic scars after burns. METHOD: A prospective study of 15 patients with post-burn hypertrophic scars was conducted between October 2016 and June 2022. All patients were treated with microneedling and drug delivery of triamcinolone. Scars were evaluated using Vancouver Scar Scale (VSS), Burn Scar Assessment Scale (BSAS) and angle measurement for amplitude of movement evaluation of joints. RESULTS: A significant improvement in the VSS score was obtained after microneedling (8.8 ± 0.44 to 4.1 ± 0.98; p = 0.012), especially in the acute group (less than 1 year after burns): 9.3 ± 0.49 to 3.5 ± 1.36; p = 0.041. There was a significant and progressive improvement of the scars throughout the treatment sessions in all criteria evaluated and in the ranges of joint movement (p = 0.012). CONCLUSION: Our microneedling protocol promoted a significant improvement of post-burn scars, especially in acute hypertrophic scars, and in the amplitude of joint motion. Sequential treatments provided progressive improvement. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Practical management of hypertrophic scarring: the mayo clinic experience.

Hypertrophic scarring is a potential consequence of wound healing that causes functional and aesthetic disability. Common treatments include intralesional pharmacotherapy (e.g., triamcinolone), surgical excision, and energy-based laser devices. While numerous treatment methods have been described for hypertrophic scarring, an optimal treatment strategy has yet to be established given variability in clinical presentation. This study aims to identify patient- and provider-preferred treatment patterns. This is a single-center, retrospective study of adult patients that developed post-surgical hypertrophic scarring between 2007 and 2017. Specifically, trends in procedural management for hypertrophic scarring among this cohort were examined. A total of 442 procedures (intralesional steroid injection, surgical excision, laser-based treatment) were identified in 218 patients with a clinical diagnosis of hypertrophic scarring. Approximately 73% were female; 87% were Caucasian. The median age at first procedure was 45.6 years (SD = 17.4). The most frequent anatomical locations for procedures were the trunk (n = 242; 54.8%), followed by head/neck (n = 86; 19.5%), upper extremities (n = 67; 15.2%), and lower extremities (n = 45; 10.2%). Procedural therapies included intralesional steroid injection (n = 221; 50%), surgical excision (n = 112; 25.3%) and laser (fractional non-ablative laser vs. pulsed dye laser; n = 109; 24.5%). Treatment modality varied by stage of treatment, scar anatomical location, and scar size. This single-center series of patients with hypertrophic scarring highlights a patient-centered management approach and offers clinical guidelines for provider-patient shared decision making.

Efficacy of Massage Techniques for Hypertrophic Burn Scars - A Systematic Review of Literature.

Despite advancements in burn care, evidence estimates that pathological scarring occurs in 32%-75% of cutaneous burns. Scar massage therapy is an under researched method of management for hypertrophic burn scars which has scope to be a low-cost treatment alternative. The aim of this systematic review was to determine the efficacy of scar massage techniques for common hypertrophic burn scar symptoms such as contraction, pruritus, pain and visibility. The keywords and corresponding MeSH terms were inputed into PubMed, EMBASE, Cochrane database of Systematic Reviews, University Library of Hull, York and Queen Mary, University of London. Following the implementation of predetermined inclusion and exclusion criteria, ten papers were included for data extraction. Quality assessment of all papers was performed using the Cochrane Risk of Bias tool and ROBINS-I tool. Data pertaining to the nature of the participant demographics, scar massage treatment, and study outcomes was extracted. Nine of the ten studies showed a significant improvement for scar massage treatment of hypertrophic burn scar symptoms despite using different massage techniques. Friction and oscillation massage was used in partnership to improve scar function, whereas effleurage and petrissage used in longer sessions was seen to improve scar visibility and pain. Scar pruritus was improved by each massage technique. Scar massage has been shown to be effective at improving scar outcomes. This paper suggests massage techniques should be tailored to the patients' symptoms. A large, randomized control trial is required to advance this area of research.

Massage, laser and shockwave therapy improve pain and scar pruritus after burns: a systematic review.

QUESTIONS: In adults with a burn injury, do non-invasive therapies improve pain and burn scar pruritus, elasticity and vascularisation? Are any effects maintained beyond the intervention period? DESIGN: Systematic review of randomised trials with meta-analyses. PARTICIPANTS: Adults with burn scars. INTERVENTION: The experimental intervention was a non-invasive (ie, non-surgical or non-pharmacological) therapy applied to the burn scar. OUTCOME MEASURES: Pain intensity, pruritus intensity, elasticity and vascularisation. RESULTS: Fifteen trials involving 780 participants were included. The results indicated a beneficial effect on pain intensity on a 0-to-10 scale after massage (MD -1.5, 95% CI -1.8 to -1.1), shockwave therapy (MD -0.8, 95% CI -1.2 to -0.4) and laser (MD -4.0, 95% CI -6.0 to -2.0). The results indicated a beneficial effect on pruritus intensity on a 0-to-10 scale after massage (MD -0.4, 95% CI -0.7 to -0.2), shockwave therapy (MD -1.3, 95% CI -2.3 to -0.3) and laser (MD -4.8, 95% CI -6.1 to -3.5). Massage, shockwave therapy and silicone produced negligible or unclear benefits on scar elasticity and vascularisation. The quality of evidence varied from low to moderate. CONCLUSION: Among all commonly used non-invasive therapies for the treatment of burn scars, low-to-moderate quality evidence indicated that massage, laser and shockwave therapy reduce pain and the intensity of scar pruritus. Low-to-moderate quality evidence suggested that massage, shockwave therapy and silicone have negligible or unclear effects for improving scar elasticity and vascularisation. REVIEW REGISTRATION: PROSPERO (CRD42021258336).

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets.

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.

Exosome Derived from Mesenchymal Stem Cells Alleviates Hypertrophic Scar by Inhibiting the Fibroblasts via TNFSF-13/HSPG2 Signaling Pathway.

Background: Mesenchymal stem cell-derived exosomes (MSC-exo) have been shown to have significant potential in wound healing and scar relief processes. According to reports, TNFSF13 and HSPG2 are associated with various fibrotic diseases. The aim of this study is to investigate how TNFSF13 and HSPG2 affect the formation of hypertrophic scar (HS) and the mechanism by which exosomes regulate HS. Methods: Immunohistochemistry, qRT-PCR, Western blot, and immunofluorescence were performed to measure TNFSF13 expression in HS skin tissues and hypertrophic scar fibroblast (HSF). HSF were treated with recombinant TNFSF13 protein and TNFSF13 siRNAs to probe the effect of TNFSF13 on the activity of HSF. The CCK-8, EdU, Transwell, and Western blot were used to investigate the role of TNFSF13 in viability, proliferation and inflammation. The influence of MSC-exo on the proliferation and function of HSF was determined by scratch and Western blot. Results: TNFSF13 was dramatically up-regulated in HS skin tissues and HSF. Recombinant TNFSF13 protein increased cell viability, proliferation, migration, fibrosis, inflammation, and the binding between TNFSF13 and HSPG2 of HSF. The opposite results were obtained in TNFSF13 siRNAs transferred HSF. Furthermore, TNFSF13 activated the nuclear factor-κB (NF-κB) signaling pathway. Silencing of HSPG2 and inhibition of NF-κB remarkably eliminated the promoting effects of TNFSF13 on cell viability, proliferation, migration, fibrosis and inflammation of HSF. MSC-exo reduced α-SMA and COL1A1 inhibited the proliferation and migration of HSF by inhibiting TNFSF13 and HSPG2. Conclusion: TNFSF13 activates NF-κB signaling pathway by interacting with HSPG2, which regulates the proliferation, migration, fibrosis and inflammatory response of HSF. Through the above mechanisms, knocking out TNFSF13 can inhibit the proliferation, migration, fibrosis and inflammatory response of HSF, whereas MSC-exo could reverse this process. These results suggest that MSC-exo alleviates HS by inhibiting the fibroblasts via TNFSF-13/HSPG2 signaling pathway.