{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:48:36Z","timestamp":1789512516089,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Pirfenidone (PFD) is a pyridine-like compound most well-known for its use in idiopathic pulmonary fibrosis (IPF). However, its broad anti-inflammatory and anti-fibrotic actions make PFD a candidate for other scarring diseases. This review examines the use of PFD for dermatologic conditions. The literature supports the potential for PFD to decrease scarring in a variety of skin conditions. Both oral and topical preparations have been shown to be effective at aiding skin healing. Early clinical evidence demonstrates significant improvements in hypertrophic burn scars, reduction in fibrosis in localized scleroderma, and accelerated epithelialization of skin graft donor sites. These clinical outcomes are supported by PFD\u2019s modulation of the transforming growth factor-beta (TGF-\u03b2) pathway, which plays a central role in skin fibrosis and scarring. Evidence in this review suggests topical PFD can be used to fill a clinical need for local anti-fibrotic therapies.<\/jats:p>","DOI":"10.3390\/medsci13030148","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pirfenidone in Skin Fibrosis and Scarring: From Bench Insights to Clinical Data"],"prefix":"10.3390","volume":"13","author":[{"given":"Kelson","family":"Knighton","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asis","family":"Babun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Turney","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brehyn","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fertala, J., Wang, M.L., Rivlin, M., Beredjiklian, P.K., Abboud, J., Arnold, W.V., and Fertala, A. (2023). Extracellular Targets to Reduce Excessive Scarring in Response to Tissue Injury. Biomolecules, 13.","DOI":"10.3390\/biom13050758"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Antar, S.A., Ashour, N.A., Marawan, M.E., and Al-Karmalawy, A.A. (2023). Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044004"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e799","DOI":"10.1111\/jdv.18277","article-title":"Prevalence of Scars: An International Epidemiological Survey in Adults","volume":"36","author":"Amici","year":"2022","journal-title":"Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Huang, C., and Ogawa, R. (2020). The Vascular Involvement in Soft Tissue Fibrosis-Lessons Learned from Pathological Scarring. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072542"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1111\/jocd.14310","article-title":"Update on Management of Keloid and Hypertrophic Scars: A Systemic Review","volume":"20","author":"Elsaie","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/1753465812436663","article-title":"Pirfenidone Treatment of Idiopathic Pulmonary Fibrosis","volume":"6","author":"Azuma","year":"2012","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_7","unstructured":"Margolin, S. (1998). Compositions and Methods for Reparation and Prevention of Fibrotic Lesions. (5,716,632), U.S. Patent."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0022-2143(98)90127-5","article-title":"Involution of Keloid Implants in Athymic Mice Treated with Pirfenidone or with Triamcinolone","volume":"132","author":"Shetlar","year":"1998","journal-title":"J. Lab. Clin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3181\/00379727-216-44187","article-title":"Pirfenidone Attenuates Bleomycin-Induced Changes in Pulmonary Functions in Hamsters","volume":"216","author":"Schelegle","year":"1997","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0940-2993(11)80261-7","article-title":"Preventive Effect of Pirfenidone against Experimental Sclerosing Peritonitis in Rats","volume":"47","author":"Suga","year":"1995","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_11","first-page":"S239","article-title":"Pirfenidone Prevents Collagen Accumulation in the Remnant Kidney in Rats with Partial Nephrectomy","volume":"63","author":"Shimizu","year":"1997","journal-title":"Kidney Int. Suppl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/jcem.83.1.4503","article-title":"Pirfenidone: A Novel Pharmacological Agent That Inhibits Leiomyoma Cell Proliferation and Collagen Production","volume":"83","author":"Lee","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0378-4274(96)03845-3","article-title":"Pirfenidone Diminishes Cyclophosphamide-Induced Lung Fibrosis in Mice","volume":"90","author":"Kehrer","year":"1997","journal-title":"Toxicol. Lett."},{"key":"ref_14","first-page":"779","article-title":"Dietary Intake of Pirfenidone Ameliorates Bleomycin-Induced Lung Fibrosis in Hamsters","volume":"125","author":"Iyer","year":"1995","journal-title":"J. Lab. Clin. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/bdd.595","article-title":"Pharmacokinetics and Metabolism of Intravenous Pirfenidone in Sheep","volume":"29","author":"Bruss","year":"2008","journal-title":"Biopharm. Drug Disp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1177\/0091270007304104","article-title":"Single-and Multiple-Dose Pharmacokinetics of Pirfenidone, an Antifibrotic Agent, in Healthy Chinese Volunteers","volume":"47","author":"Shi","year":"2007","journal-title":"J. Clin. Pharma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1055\/s-0033-1341478","article-title":"Pharmacokinetics, Safety and Tolerability of Pirfenidone and Its Major Metabolite after Single and Multiple Oral Doses in Healthy Chinese Subjects under Fed Conditions","volume":"63","author":"Huang","year":"2013","journal-title":"Drug Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejps.2014.02.014","article-title":"Effect of Pirfenidone on Proliferation, TGF-\u03b2-Induced Myofibroblast Differentiation and Fibrogenic Activity of Primary Human Lung Fibroblasts","volume":"58","author":"Conte","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F52","DOI":"10.1152\/ajprenal.00260.2018","article-title":"Macrophage-Secreted TGF-\u03921 Contributes to Fibroblast Activation and Ureteral Stricture after Ablation Injury","volume":"317","author":"Ueshima","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1165\/rcmb.2019-0328TR","article-title":"Pirfenidone: Molecular Mechanisms and Potential Clinical Applications in Lung Disease","volume":"62","author":"Ruwanpura","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/resp.12487","article-title":"Combination Pirfenidone and Inhaled N-acetylcysteine Therapy for IPF: Does It Take These Two to Tango?","volume":"20","author":"Velez","year":"2015","journal-title":"Respirology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Finnerty, J.P., Ponnuswamy, A., Dutta, P., Abdelaziz, A., and Kamil, H. (2021). Efficacy of Antifibrotic Drugs, Nintedanib and Pirfenidone, in Treatment of Progressive Pulmonary Fibrosis in Both Idiopathic Pulmonary Fibrosis (IPF) and Non-IPF: A Systematic Review and Meta-Analysis. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01783-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1208\/s12249-023-02618-4","article-title":"Pulmonary Fibrosis: Unveiling the Pathogenesis, Exploring Therapeutic Targets, and Advancements in Drug Delivery Strategies","volume":"24","author":"Aggarwal","year":"2023","journal-title":"AAPS PharmSciTech"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1335","DOI":"10.1002\/iid3.1335","article-title":"Pirfenidone Use in Fibrotic Diseases: What Do We Know so Far?","volume":"12","author":"Torre","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_25","unstructured":"Knighton, K., Babun, A., Evans, B., Turney, J., and Sehgal, I. (2024, January 8). Pirfenidone: A Review of its Dermatologic Uses. Proceedings of the 2nd Annual Dermatology Therapeutics Symposium, Austin, TX, USA."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s12325-014-0112-1","article-title":"Pirfenidone in Idiopathic Pulmonary Fibrosis: Expert Panel Discussion on the Management of Drug-Related Adverse Events","volume":"31","author":"Costabel","year":"2014","journal-title":"Adv. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/S0140-6736(11)60405-4","article-title":"Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (CAPACITY): Two Randomised Trials","volume":"377","author":"Noble","year":"2011","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1208\/s12249-018-1030-3","article-title":"Development of a Topical 48-H Release Formulation as an Anti-Scarring Treatment for Deep Partial-Thickness Burns","volume":"19","author":"Dorati","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chung, E.P., Nguyen, J.Q., Tellkamp-Schehr, T., Goebel, K., Ollek, A., Krein, C., Wells, A.R., Sebastian, E.A., Goebel, A., and Niese, S. (2023). A Soft Skin Adhesive (SSA) Patch for Extended Release of Pirfenidone in Burn Wounds. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071842"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1039\/C9TB02929J","article-title":"A Pirfenidone Loaded Spray Dressing Based on Lyotropic Liquid Crystals for Deep Partial Thickness Burn Treatment: Healing Promotion and Scar Prophylaxis","volume":"8","author":"Chen","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_31","first-page":"29787","article-title":"Multilayer Injectable Hydrogel System Sequentially Delivers Bioactive Substances for Each Wound Healing Stage","volume":"12","author":"Ma","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/SAP.0b013e31821b6d08","article-title":"A Controlled Clinical Trial with Pirfenidone in the Treatment of Pathological Skin Scarring Caused by Burns in Pediatric Patients","volume":"68","author":"Miranda","year":"2012","journal-title":"Ann. Plast. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ejps.2015.12.027","article-title":"Effect of Pirfenidone Delivered Using Layer-by-Layer Thin Film on Excisional Wound Healing","volume":"83","author":"Mandapalli","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_34","first-page":"S170","article-title":"Efficacy of Pirfenidone in Post-Dermal Burns Hypertrophic Scars: A Multicenter Experience","volume":"33","author":"Medina","year":"2012","journal-title":"J. Burn Care Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"He, J., Meng, X., Meng, C., Zhao, J., Chen, Y., Zhang, Z., and Zhang, Y. (2022). Layer-by-Layer Pirfenidone\/Cerium Oxide Nanocapsule Dressing Promotes Wound Repair and Prevents Scar Formation. Molecules, 27.","DOI":"10.3390\/molecules27061830"},{"key":"ref_36","first-page":"510","article-title":"Pirfenidone Gel in Patients with Localized Scleroderma: A Phase II Study","volume":"16","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_37","unstructured":"P.R. Vademecum (2024, November 02). Kitoscell: Cell Pharma. Available online: https:\/\/mx.prvademecum.com\/medicamento\/kitoscell-13244\/."},{"key":"ref_38","unstructured":"(2024, August 27). DailyMed-ESBRIET-Pirfenidone Capsule ESBRIET-Pirfenidone Tablet, Coated, Available online: https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=2e8c3537-36d7-4de5-9b5c-7a624b9a9e6e."},{"key":"ref_39","first-page":"169","article-title":"Effects of Pirfenidone on the Generation of Reactive Oxygen Species in Vitro","volume":"18","author":"Giri","year":"1999","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, B., Qiao, Y., Yan, D., and Meng, Q. (2024). Targeting Interactions between Fibroblasts and Macrophages to Treat Cardiac Fibrosis. Cells, 13.","DOI":"10.3390\/cells13090764"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Evani, S.J., Karna, S.R., Seshu, J., and Leung, K.P. (2020). Pirfenidone Regulates LPS Mediated Activation of Neutrophils. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76271-3"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1165\/rcmb.2020-0387OC","article-title":"Antifibrotics Modify B-Cell-Induced Fibroblast Migration and Activation in Patients with Idiopathic Pulmonary Fibrosis","volume":"64","author":"Ali","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_43","first-page":"1593","article-title":"Pirfenidone Inhibits Epidural Scar Fibroblast Proliferation and Differentiation by Regulating TGF-\u03921-Induced Smad-Dependent and -Independent Pathways","volume":"11","author":"Shi","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liarte, S., Bernab\u00e9-Garc\u00eda, \u00c1., and Nicol\u00e1s, F.J. (2020). Role of TGF-\u03b2 in Skin Chronic Wounds: A Keratinocyte Perspective. Cells, 9.","DOI":"10.3390\/cells9020306"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00403-011-1184-2","article-title":"Pirfenidone Suppresses Keloid Fibroblast-Embedded Collagen Gel Contraction","volume":"304","author":"Saito","year":"2012","journal-title":"Arch. Dermatol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S239","DOI":"10.1093\/jbcr\/irz013.415","article-title":"Pirfenidone Inhibits Epithelial-Mesenchymal Transition (EMT) Genes in Keloid Keratinocytes","volume":"40","author":"Evdokiou","year":"2019","journal-title":"J. Burn Care Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41374-017-0014-3","article-title":"Pirfenidone Reduces Profibrotic Responses in Human Dermal Myofibroblasts, in Vitro","volume":"98","author":"Hall","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.bbrc.2019.10.177","article-title":"Pirfenidone Attenuates the Profibrotic Contractile Phenotype of Differentiated Human Dermal Myofibroblasts","volume":"521","author":"Wells","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1007\/s11010-023-04912-y","article-title":"Drugs Targeting TGF-\u03b2\/Notch Interaction Attenuate Hypertrophic Scar Formation by Optic Atrophy 1-Mediated Mitochondrial Fusion","volume":"479","author":"Huo","year":"2023","journal-title":"Mol. Cell Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dai, Z.H., Jiang, Y.W., Guo, H., Lu, Y.T., Chen, W.G., and Liang, T. (2025). Pirfenidone Ameliorates Hypertrophic Scar Through Inhibiting Proliferation and Migration of Fibroblasts by Regulating the Wnt\/GSK-3\u03b2\/\u03b2-Catenin Signaling Pathway. J. Burn Care Res.","DOI":"10.1093\/jbcr\/iraf040"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Coentro, J.Q., May, U., Prince, S., Zwaagstra, J., Ritvos, O., J\u00e4rvinen, T.A., and Zeugolis, D.I. (2021). Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.756399"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1016\/j.burns.2018.07.007","article-title":"Pirfenidone Increases the Epithelialization Rate of Skin Graft Donor Sites","volume":"44","author":"Bracho","year":"2018","journal-title":"Burns"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.ASW.0000655484.95155.f7","article-title":"Efficacy and Safety of Pirfenidone in Patients with Second-Degree Burns: A Proof-of-Concept Randomized Controlled Trial","volume":"33","author":"Mecott","year":"2020","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"tkz007","DOI":"10.1093\/burnst\/tkz007","article-title":"Pirfenidone Inhibits Epithelial-Mesenchymal Transition in Keloid Keratinocytes","volume":"8","author":"Satish","year":"2020","journal-title":"Burn. Trauma"},{"key":"ref_55","first-page":"192","article-title":"Kitoscell r in the Treatment of Scars after Burn Injuries, Long-Term Follow-Up","volume":"29","author":"David","year":"2020","journal-title":"J. Wound Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1097\/SCS.0b013e31828609cb","article-title":"Coadjuvant Treatment with Surgery and Pirfenidone in Severe Facial Trauma Due to Dog Bite","volume":"24","year":"2013","journal-title":"J. Craniofac. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.3899\/jrheum.081284","article-title":"The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress toward Development of Localized Scleroderma Outcome Measures","volume":"36","author":"Arkachaisri","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chipp, E., Charles, L., Thomas, C., Whiting, K., Moiemen, N., and Wilson, Y. (2017). A Prospective Study of Time to Healing and Hypertrophic Scarring in Paediatric Burns: Every Day Counts. Burn. Trauma, 5.","DOI":"10.1186\/s41038-016-0068-2"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zhou, S., Xie, M., Su, J., Cai, B., Li, J., and Zhang, K. (2023). New Insights into Balancing Wound Healing and Scarless Skin Repair. J. Tissue Eng., 14.","DOI":"10.1177\/20417314231185848"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.5021\/ad.21.052","article-title":"A Case of Pirfenidone Induced Photosensitive Drug Eruption","volume":"35","author":"Jeong","year":"2023","journal-title":"Ann. Dermatol."},{"key":"ref_61","first-page":"225","article-title":"RP-HPLC and UV Spectrophotometric Methods for Estimation of Pirfenidone in Pharmaceutical Formulations","volume":"76","author":"Parmar","year":"2014","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1038\/s41467-021-24110-y","article-title":"Single-Cell RNA-Seq Reveals Fibroblast Heterogeneity and Increased Mesenchymal Fibroblasts in Human Fibrotic Skin Diseases","volume":"12","author":"Deng","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cheng, X., Gao, Z., Shan, S., Shen, H., Zheng, H., Jin, L., Li, Q., and Zhou, J. (2024). Single Cell Transcriptomics Reveals the Cellular Heterogeneity of Keloids and the Mechanism of Their Aggressiveness. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-07311-1"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Liu, Z., Bian, X., Luo, L., Bj\u00f6rklund, \u00c5.K., Li, L., Zhang, L., Chen, Y., Guo, L., Gao, J., and Cao, C. (2025). Spatiotemporal Single-Cell Roadmap of Human Skin Wound Healing. Cell Stem Cell, 32.","DOI":"10.1101\/2024.08.30.609923"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1039\/D1MD00403D","article-title":"Synthesis and Structure\u2013Activity Relationships of Pirfenidone Derivatives as Anti-Fibrosis Agents in Vitro","volume":"13","author":"Shi","year":"2022","journal-title":"RSC Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cai, X., Liu, X., Xie, W., Ma, A., Tan, Y., Shang, J., Zhang, J., Chen, C., Yu, Y., and Qu, Y. (2023). Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial. Clin. Gastroenterol. Hepatol., 21.","DOI":"10.1016\/j.cgh.2022.05.056"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lu, X., Zhu, C., Gao, Y., Yu, Z., Yan, Q., Liu, Y., Luo, M., and Shi, X. (2024). Design, Synthesis, and Evaluation of Pirfenidone-NSAIDs Conjugates for the Treatment of Idiopathic Pulmonary Fibrosis. Bioorg. Chem., 143.","DOI":"10.1016\/j.bioorg.2023.107018"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/jm501562a","article-title":"Nintedanib: From Discovery to the Clinic","volume":"58","author":"Roth","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Wong, T.-S., Li, J.Z.-H., Chen, S., Chan, J.Y.-W., and Gao, W. (2016). The Efficacy of Triamcinolone Acetonide in Keloid Treatment: A Systematic Review and Meta-Analysis. Front. Med., 3.","DOI":"10.3389\/fmed.2016.00071"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2147\/CCID.S133672","article-title":"Triamcinolone Acetonide Intralesional Injection for the Treatment of Keloid Scars: Patient Selection and Perspectives","volume":"11","author":"Salzillo","year":"2018","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/iwj.13337","article-title":"Efficacy of Topical Silicone Gel in Scar Management: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"17","author":"Wang","year":"2020","journal-title":"Int. Wound J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"128","DOI":"10.22467\/jwmr.2024.02887","article-title":"Increased Patient Compliance with Silicone Gel Sheeting and Topical Silicone Gel for Hypertrophic Scar Improves Scar Outcomes","volume":"20","author":"Cho","year":"2024","journal-title":"J. Wound Manag. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1097\/SAP.0000000000003712","article-title":"Treatment of Hypertrophic Burn Scars With Laser Therapy: A Review of Adverse Events","volume":"91","author":"Won","year":"2023","journal-title":"Ann. Plast. Surg."},{"key":"ref_74","first-page":"CD011642","article-title":"Laser Therapy for Treating Hypertrophic and Keloid Scars","volume":"9","author":"Leszczynski","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_75","unstructured":"UpToDate (2024). Pirfenidone: Drug Information (Pricing). UpToDate Lexidrug, Wolters Kluwer."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:31:57Z","timestamp":1760034717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/13\/3\/148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":75,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["medsci13030148"],"URL":"https:\/\/doi.org\/10.3390\/medsci13030148","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}