{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T07:45:53Z","timestamp":1788594353524,"version":"build-2803163510"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Hypertrophic scar (HS) is a typical pathological response during skin injury, which can lead to pain, itching, and contracture in patients and even affect their physical and mental health. The complexity of the wound healing process leads to the formation of HS affected by many factors. Several treatments are available for HS, whereas some have more adverse reactions and can even cause new injuries with exacerbated scarring. Traditional Chinese Medicine (TCM) has a rich source, and most botanical drugs have few side effects, providing new ideas and methods for treating HS. This paper reviews the formation process of HS, the therapeutic strategy for HS, the research progress of TCM with its relevant mechanisms in the treatment of HS, and the related new drug delivery system of TCM, aiming to provide ideas for further research of botanical compounds in the treatment of HS, to promote the discovery of more efficient botanical candidates for the clinical treatment of HS, to accelerate the development of the new drug delivery system and the final clinical application, and at the same time, to promote the research on the anti-HS mechanism of multiherbal preparations (Fufang), to continuously improve the quality control and safety and effectiveness of anti-HS botanical drugs in clinical application.<\/jats:p>","DOI":"10.3389\/fphar.2022.1025602","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T06:45:50Z","timestamp":1665384350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Traditional Chinese medicine for hypertrophic scars\u2014A review of the therapeutic methods and potential effects"],"prefix":"10.3389","volume":"13","author":[{"given":"Daqin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1046\/j.1524-4725.2003.29024.x","article-title":"Laser scar revision: Comparison study of 585-nm pulsed dye laser with and without intralesional corticosteroids","volume":"29","author":"Alster","year":"2003","journal-title":"Dermatol. Surg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.12968\/bjcn.2019.24.Sup9.S26","article-title":"Chronic wounds: The challenges of appropriate management","volume":"24","author":"Atkin","year":"2019","journal-title":"Br. J. Community Nurs."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2950","DOI":"10.12659\/msm.916305","article-title":"Intralesional injection of botulinum toxin type A compared with intralesional injection of corticosteroid for the treatment of hypertrophic scar and keloid: A systematic review and meta-analysis","volume":"25","author":"Bi","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"B4","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/s0889-1591(02)00021-1","article-title":"Stress and the inflammatory response: A review of neurogenic inflammation","volume":"16","author":"Black","year":"2002","journal-title":"Brain Behav. Immun."},{"key":"B5","first-page":"159","article-title":"Chronic wounds: Evaluation and management","volume":"101","author":"Bowers","year":"2020","journal-title":"Am. Fam. Physician"},{"key":"B6","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s12272-011-0405-8","article-title":"A combination of a microemulsion and a phospholipid complex for topical delivery of oxymatrine","volume":"34","author":"Cao","year":"2011","journal-title":"Arch. Pharm. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1097\/bcr.0000000000000413","article-title":"Elastin is differentially regulated by pressure therapy in a porcine model of hypertrophic scar","volume":"38","author":"Carney","year":"2017","journal-title":"J. Burn Care Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1111\/j.1524-4725.2004.30303.x","article-title":"The use of pulsed dye laser for the prevention and treatment of hypertrophic scars in Chinese persons","volume":"30","author":"Chan","year":"2004","journal-title":"Dermatol. Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1002\/lsm.23092","article-title":"Efficacy of combined intense pulsed light (ipl) with fractional CO(2) -laser ablation in the treatment of large hypertrophic scars: A prospective, randomized control trial","volume":"51","author":"Daoud","year":"2019","journal-title":"Lasers Surg. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1089\/wound.2020.1161","article-title":"Improved scar outcomes with increased daily duration of pressure garment therapy","volume":"9","author":"DeBruler","year":"2020","journal-title":"Adv. Wound Care"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1111\/iwj.13717","article-title":"Oxymatrine promotes hypertrophic scar repair through reduced human scar fibroblast viability, collagen and induced apoptosis via autophagy inhibition","volume":"19","author":"Deng","year":"2021","journal-title":"Int. Wound J."},{"key":"B12","doi-asserted-by":"publisher","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":"B13","doi-asserted-by":"publisher","first-page":"265sr6","DOI":"10.1126\/scitranslmed.3009337","article-title":"Wound repair and regeneration: Mechanisms, signaling, and translation","volume":"6","author":"Eming","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.burns.2010.04.014","article-title":"12-Year within-wound study of the effectiveness of custom pressure garment therapy","volume":"36","author":"Engrav","year":"2010","journal-title":"Burns"},{"key":"B15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00266-007-9109-3","article-title":"Treatment of postdermabrasion facial hypertrophic and keloid scars with intralesional 5-Fluorouracil injections","volume":"32","author":"Goldan","year":"2008","journal-title":"Aesthetic Plast. Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.3390\/cells10071729","article-title":"The role of MSC in wound healing, scarring and regeneration","volume":"10","author":"Guillamat-Prats","year":"2021","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","first-page":"4857","DOI":"10.19540\/j.cnki.cjcmm.20190901.301","article-title":"Study on physicochemical properties of paeonol-Helix aspersa muller nanogel and its inhibitory effects on hypertrophic scar tissue in rabbit ear","volume":"44","author":"Guo","year":"2019","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B18","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1590\/abd1806-4841.20176656","article-title":"Wound natural healing in treatment of tumor-like hypertrophic scar","volume":"92","author":"Han","year":"2017","journal-title":"An. Bras. Dermatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1097\/01.Prs.0000056868.42679.05","article-title":"Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids","volume":"111","author":"Har-Shai","year":"2003","journal-title":"Plast. Reconstr. Surg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/PRS.0b013e3181904d1b","article-title":"5-Fluorouracil treatment of problematic scars","volume":"123","author":"Haurani","year":"2009","journal-title":"Plast. Reconstr. Surg."},{"key":"B21","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/iwj.13561","article-title":"Inhibition of hypertrophic scar formation with oral asiaticoside treatment in a rabbit ear scar model","volume":"18","author":"Huang","year":"2021","journal-title":"Int. Wound J."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.2147\/tcrm.S82961","article-title":"Paclitaxel reduces formation of hypertrophic scars in the rabbit ear model","volume":"11","author":"Huang","year":"","journal-title":"Ther. Clin. Risk Manag."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.2174\/1389450116666150309122334","article-title":"Nano traditional Chinese medicine: Current progresses and future challenges","volume":"16","author":"Huang","year":"","journal-title":"Curr. Drug Targets"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4783","DOI":"10.3892\/mmr.2020.11539","article-title":"Arctigenin suppresses fibroblast activity and extracellular matrix deposition in hypertrophic scarring by reducing inflammation and oxidative stress","volume":"22","author":"Jiang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3892\/etm.2021.10289","article-title":"Emodin ameliorates acute pancreatitis-induced lung injury by suppressing NLRP3 inflammasome-mediated neutrophil recruitment","volume":"22","author":"Jiang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/j.1600-0560.2008.01015.x","article-title":"Effect of asiaticoside on hypertrophic scar in the rabbit ear model","volume":"36","author":"Ju-Lin","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1097\/prs.0000000000001507","article-title":"Burn scar biomechanics after pressure garment therapy","volume":"136","author":"Kim","year":"2015","journal-title":"Plast. Reconstr. Surg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/sj.bjp.0706794","article-title":"Effects of ginseng saponins isolated from Red Ginseng roots on burn wound healing in mice","volume":"148","author":"Kimura","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"tkz002","DOI":"10.1093\/burnst\/tkz002","article-title":"Laser management of hypertrophic burn scars: A comprehensive review","volume":"8","author":"Klifto","year":"2020","journal-title":"Burns Trauma"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e272","DOI":"10.1097\/gox.0000000000000231","article-title":"Nd:YAG laser treatment for keloids and hypertrophic scars: An analysis of 102 cases","volume":"2","author":"Koike","year":"2014","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"B31","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.intimp.2015.10.023","article-title":"Icariin inhibits TNF-\u03b1\/IFN-\u03b3 induced inflammatory response via inhibition of the substance P and p38-MAPK signaling pathway in human keratinocytes","volume":"29","author":"Kong","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.burns.2020.07.008","article-title":"The therapeutic effect of Interleukin-18 on hypertrophic scar through inducing Fas ligand expression","volume":"47","author":"Le","year":"2021","journal-title":"Burns."},{"key":"B33","doi-asserted-by":"publisher","first-page":"E711","DOI":"10.3390\/ijms19030711","article-title":"Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids","volume":"19","author":"Lee","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.phymed.2012.08.002","article-title":"Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model","volume":"19","author":"Lee","year":"2012","journal-title":"Phytomedicine"},{"key":"B35","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1097\/BCR.0b013e3181eebea0","article-title":"Pressure prediction model for compression garment design","volume":"31","author":"Leung","year":"2010","journal-title":"J. Burn Care Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13075-019-1876-0","article-title":"Baicalein ameliorates pristane-induced lupus nephritis via activating Nrf2\/HO-1 in myeloid-derived suppressor cells","volume":"21","author":"Li","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.2147\/ijn.S241923","article-title":"Preparation and in vitro and in vivo study of asiaticoside-loaded nanoemulsions and nanoemulsions-based gels for transdermal delivery","volume":"15","author":"Li","year":"2020","journal-title":"Int. J. Nanomedicine"},{"key":"B38","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.biopha.2016.08.011","article-title":"Kaempferol inhibits fibroblast collagen synthesis, proliferation and activation in hypertrophic scar via targeting TGF-\u03b2 receptor type I","volume":"83","author":"Li","year":"","journal-title":"Biomed. Pharmacother."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/j.burns.2018.01.008","article-title":"The recovery of post-burn hypertrophic scar in a monitored pressure therapy intervention programme and the timing of intervention","volume":"44","author":"Li","year":"2018","journal-title":"Burns"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.4103\/1673-5374.167769","article-title":"Inflammation and cutaneous nervous system involvement in hypertrophic scarring","volume":"10","author":"Li","year":"2015","journal-title":"Neural Regen. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.3892\/etm.2021.10509","article-title":"Emodin inhibits the proliferation of papillary thyroid carcinoma by activating AMPK","volume":"22","author":"Li","year":"","journal-title":"Exp. Ther. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.biopha.2016.03.006","article-title":"Cryptotanshinone downregulates the profibrotic activities of hypertrophic scar fibroblasts and accelerates wound healing: A potential therapy for the reduction of skin scarring","volume":"80","author":"Li","year":"","journal-title":"Biomed. Pharmacother."},{"key":"B43","doi-asserted-by":"publisher","first-page":"119483","DOI":"10.1016\/j.lfs.2021.119483","article-title":"Corilagin alleviates hypertrophic scars via inhibiting the transforming growth factor (TGF)-\u03b2\/Smad signal pathway","volume":"277","author":"Li","year":"","journal-title":"Life Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s13287-021-02290-0","article-title":"Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p\/IL-17RA\/Smad axis","volume":"12","author":"Li","year":"","journal-title":"Stem Cell Res. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"11831","DOI":"10.1038\/s41598-018-29840-6","article-title":"RNA-seq-based analysis of the hypertrophic scarring with and without pressure therapy in a Bama minipig model","volume":"8","author":"Liu","year":"2018","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.3892\/mmr.2015.3265","article-title":"Inhibition of mechanical stress-induced hypertrophic scar inflammation by emodin","volume":"11","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1093\/jbcr\/irz056","article-title":"Treating hypertrophic burn scar with 2940-nm Er:YAG laser fractional ablation improves scar characteristics as measured by noninvasive technology","volume":"40","author":"Madni","year":"2019","journal-title":"J. Burn Care Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1111\/iwj.12944","article-title":"An intra-individual surgical wound comparison shows that octenidine-based hydrogel wound dressing ameliorates scar appearance following abdominoplasty","volume":"15","author":"Matiasek","year":"2018","journal-title":"Int. Wound J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1111\/exd.12723","article-title":"Microneedle applications in improving skin appearance","volume":"24","author":"McCrudden","year":"2015","journal-title":"Exp. Dermatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.abd.2020.08.019","article-title":"Tacrolimus action pathways in an ointment base for hypertrophic scar prevention in a rabbit ear model","volume":"96","author":"Menezes","year":"2021","journal-title":"An. Bras. Dermatol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.phrp.2016.08.005","article-title":"Comparing two methods of cryotherapy and intense pulsed light with triamcinolone injection in the treatment of keloid and hypertrophic scars: A clinical trial","volume":"7","author":"Meymandi","year":"2016","journal-title":"Osong Public Health Res. Perspect."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e574","DOI":"10.1097\/sla.0000000000003576","article-title":"Fractional ablative laser therapy is an effective treatment for hypertrophic burn scars: A prospective study of objective and subjective outcomes","volume":"274","author":"Miletta","year":"2021","journal-title":"Ann. Surg."},{"key":"B53","doi-asserted-by":"publisher","first-page":"12222","DOI":"10.1038\/s41598-022-16376-z","article-title":"Angiogenic gene characterization and vessel permeability of dermal microvascular endothelial cells isolated from burn hypertrophic scar","volume":"12","author":"Molina","year":"2022","journal-title":"Sci. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/wrr.12937","article-title":"Myofibroblast progeny in wound biology and wound healing studies","volume":"29","author":"Monika","year":"2021","journal-title":"Wound Repair Regen."},{"key":"B55","doi-asserted-by":"publisher","first-page":"XVi","DOI":"10.12968\/jowc.2021.30.Sup9a.XV","article-title":"The effects of kiwifruit dressing on hypertrophic scars in a rabbit ear model","volume":"30","author":"Mousavizadeh","year":"2021","journal-title":"J. Wound Care"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4238\/gmr.15017288","article-title":"Tetrandrine induces microRNA differential expression in human hypertrophic scar fibroblasts in vitro","volume":"15","author":"Ning","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.1016\/j.apsb.2021.03.016","article-title":"Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment","volume":"11","author":"Ning","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"B58","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1272\/jnms.83.46","article-title":"Keloids and hypertrophic scars can now Be cured completely: Recent progress in our understanding of the pathogenesis of keloids and hypertrophic scars and the most promising current therapeutic strategy","volume":"83","author":"Ogawa","year":"2016","journal-title":"J. Nippon. Med. Sch."},{"key":"B59","doi-asserted-by":"publisher","first-page":"4969","DOI":"10.2147\/ijn.S252027","article-title":"Polyphenol-conjugated bimetallic Au@AgNPs for improved wound healing","volume":"15","author":"Orlowski","year":"2020","journal-title":"Int. J. Nanomedicine"},{"key":"B60","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.3892\/mmr.2020.11407","article-title":"Resveratrol inhibits hypertrophic scars formation by activating autophagy via the miR-4654\/Rheb axis","volume":"22","author":"Pang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1097\/01.Ta.0000030630.72836.32","article-title":"Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro: Therapeutic implication for excessive scarring","volume":"54","author":"Phan","year":"2003","journal-title":"J. Trauma"},{"key":"B62","doi-asserted-by":"publisher","first-page":"12614","DOI":"10.3390\/ijms222312614","article-title":"Resveratrol-induced signal transduction in wound healing","volume":"22","author":"Pignet","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1080\/15548627.2020.1816342","article-title":"Keratinocyte autophagy enables the activation of keratinocytes and fibroblastsand facilitates wound healing","volume":"17","author":"Qiang","year":"2021","journal-title":"Autophagy"},{"key":"B64","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s10103-020-03120-0","article-title":"Efficacy and safety of Nd:YAG laser alone compared with combined Nd:YAG laser with intralesional steroid or botulinum toxin A in the treatment of hypertrophic scars","volume":"36","author":"Rahman","year":"2021","journal-title":"Lasers Med. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2444839","DOI":"10.1155\/2021\/2444839","article-title":"Bioflavonoid galangin suppresses hypertrophic scar formation by the TGF-\u03b2\/smad signaling pathway","volume":"2021","author":"Ru","year":"2021","journal-title":"Evid. Based. Complement. Altern. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.1111\/jocd.13971","article-title":"Intense pulsed light versus cryotherapy in the treatment of hypertrophic scars: A clinical and histopathological study","volume":"20","author":"Salem","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1111\/j.1524-475X.2007.00222.x","article-title":"Making sense of hypertrophic scar: A role for nerves","volume":"15","author":"Scott","year":"2007","journal-title":"Wound Repair Regen."},{"key":"B68","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","article-title":"Human skin wounds: A major and snowballing threat to public health and the economy","volume":"17","author":"Sen","year":"2009","journal-title":"Wound Repair Regen."},{"key":"B69","doi-asserted-by":"publisher","first-page":"4643","DOI":"10.3892\/mmr.2017.7209","article-title":"Naringenin attenuates fibroblast activation and inflammatory response in a mechanical stretch-induced hypertrophic scar mouse model","volume":"16","author":"Shan","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/08982104.2019.1593451","article-title":"Behaviour of cell penetrating peptide TAT-modified liposomes loaded with salvianolic acid B on the migration, proliferation, and survival of human skin fibroblasts","volume":"30","author":"Shi","year":"2020","journal-title":"J. Liposome Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1111\/jocd.12690","article-title":"Comparative efficacy of intralesional triamcinolone acetonide injection during early and static stage of pathological scarring","volume":"18","author":"Song","year":"2019","journal-title":"J. Cosmet. Dermatol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1159\/000490417","article-title":"Quercetin shows the pharmacological activity to simultaneously downregulate the inflammatory and fibrotic responses to tissue injury in association with its ability to target multi-kinases","volume":"102","author":"Song","year":"","journal-title":"Pharmacology"},{"key":"B73","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.biopha.2018.06.176","article-title":"Usnic acid inhibits hypertrophic scarring in a rabbit ear model by suppressing scar tissue angiogenesis","volume":"108","author":"Song","year":"","journal-title":"Biomed. Pharmacother."},{"key":"B74","doi-asserted-by":"publisher","first-page":"6486","DOI":"10.3390\/ijms22126486","article-title":"The role of calcium in wound healing","volume":"22","author":"Subramaniam","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e008888-19","DOI":"10.1128\/aac.00888-19","article-title":"Evaluation of the antifungal and wound-healing properties of a novel peptide-based bioadhesive hydrogel formulation","volume":"63","author":"Sultan","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B76","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/lsm.23301","article-title":"Hypertrophic scar improvement by early intervention with ablative fractional carbon dioxide laser treatment","volume":"53","author":"Tan","year":"2021","journal-title":"Lasers Surg. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"309","DOI":"10.22038\/ijbms.2018.19451.5153","article-title":"The inhibitory effects of 20(R)-ginsenoside Rg3 on the proliferation, angiogenesis, and collagen synthesis of hypertrophic scar derived fibroblasts in vitro","volume":"21","author":"Tang","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"9381","DOI":"10.1073\/pnas.1810133115","article-title":"Substance P and IL-33 administered together stimulate a marked secretion of IL-1\u03b2 from human mast cells, inhibited by methoxyluteolin","volume":"115","author":"Taracanova","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B79","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ejphar.2015.01.011","article-title":"Effects of ginsenoside Rb1 on hypertrophic scar remodeling in rabbit model","volume":"750","author":"Tark","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"173","DOI":"10.2147\/ccid.S191137","article-title":"Topical 5 fluorouracil cream vs combined 5 fluorouracil and fractional erbium YAG laser for treatment of severe hypertrophic scars","volume":"12","author":"Tawfik","year":"2019","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"57","DOI":"10.15570\/actaapa.2019.15","article-title":"Cryosurgery to remove perichondrium for the rabbit ear hypertrophic scar model: A simplified method","volume":"28","author":"Tunca","year":"2019","journal-title":"Acta dermatovenerol. Alp. Pannonica Adriat."},{"key":"B82","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.burns.2005.04.014","article-title":"The assessment of erythema and thickness on burn related scars during pressure garment therapy as a preventive measure for hypertrophic scarring","volume":"31","author":"Van den Kerckhove","year":"2005","journal-title":"Burns"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1016\/j.bjps.2014.08.046","article-title":"A new argon gas-based device for the treatment of keloid scars with the use of intralesional cryotherapy","volume":"67","author":"van Leeuwen","year":"2014","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"B84","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.addr.2018.09.010","article-title":"Therapeutic strategies for enhancing angiogenesis in wound healing","volume":"146","author":"Veith","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B85","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1097\/dss.0000000000001678","article-title":"Treatment of hypertrophic scars using laser-assisted corticosteroid versus laser-assisted 5-fluorouracil delivery","volume":"45","author":"Waibel","year":"2019","journal-title":"Dermatol. Surg."},{"key":"B86","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.jcma.2017.11.002","article-title":"Wound healing","volume":"81","author":"Wang","year":"","journal-title":"J. Chin. Med. Assoc."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1093\/abbs\/gmy115","article-title":"Gallic acid inhibits fibroblast growth and migration in keloids through the AKT\/ERK signaling pathway","volume":"50","author":"Wang","year":"","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"B88","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1111\/wrr.12913","article-title":"LncRNA MIR503HG promotes hypertrophic scar progression via miR-143-3p-mediated Smad3 expression","volume":"29","author":"Wei","year":"2021","journal-title":"Wound Repair Regen."},{"key":"B89","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3109\/13880209.2010.542761","article-title":"Inhibitory effects of essential oil from rhizomes of Ligusticum chuanxiong on hypertrophic scarring in the rabbit ear model","volume":"49","author":"Wu","year":"2011","journal-title":"Pharm. Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"20087","DOI":"10.1021\/acsnano.1c07829","article-title":"Microneedle-mediated biomimetic cyclodextrin metal organic frameworks for active targeting and treatment of hypertrophic scars","volume":"15","author":"Wu","year":"2021","journal-title":"ACS Nano"},{"key":"B91","doi-asserted-by":"publisher","first-page":"602","DOI":"10.3389\/fphar.2020.00602","article-title":"Tetramethylpyrazine induces apoptosis and inhibits proliferation of hypertrophic scar-derived fibroblasts via inhibiting the phosphorylation of AKT","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1097\/wnr.0000000000001199","article-title":"Puerarin suppresses TRPV1, calcitonin gene-related peptide and substance P to prevent paclitaxel-induced peripheral neuropathic pain in rats","volume":"30","author":"Wu","year":"2019","journal-title":"Neuroreport"},{"key":"B93","doi-asserted-by":"publisher","first-page":"e11184","DOI":"10.1590\/1414-431X2021e11184","article-title":"Emodin alleviates hypertrophic scar formation by suppressing macrophage polarization and inhibiting the Notch and TGF-\u03b2 pathways in macrophages","volume":"54","author":"Xia","year":"2021","journal-title":"Braz J. Med. Biol. Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1002\/jbm.b.34830","article-title":"Poly (\u03b3-glutamic acid)\/chitooligo-saccharide\/papain hydrogel prevents hypertrophic scar during skin wound healing","volume":"109","author":"Xue","year":"2021","journal-title":"J. Biomed. Mat. Res. B Appl. Biomater."},{"key":"B95","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.1016\/j.bioactmat.2021.01.014","article-title":"Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy","volume":"6","author":"Yang","year":"","journal-title":"Bioact. Mat."},{"key":"B96","doi-asserted-by":"publisher","first-page":"4262","DOI":"10.2337\/db14-0163","article-title":"Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor","volume":"63","author":"Yang","year":"2014","journal-title":"Diabetes"},{"key":"B97","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1080\/21691401.2019.1645150","article-title":"Baicalein inhibits proliferation and collagen synthesis of mice fibroblast cell line NIH\/3T3 by regulation of miR-9\/insulin-like growth factor-1 axis","volume":"47","author":"Yang","year":"","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"15625","DOI":"10.1002\/jcb.28829","article-title":"Baicalein retards proliferation and collagen deposition by activating p38MAPK-JNK via microRNA-29","volume":"120","author":"Yang","year":"","journal-title":"J. Cell. Biochem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"tkab008","DOI":"10.1093\/burnst\/tkab008","article-title":"Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization","volume":"9","author":"Yang","year":"","journal-title":"Burns Trauma"},{"key":"B100","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ejphar.2019.02.039","article-title":"Dihydromyricetin attenuates hypertrophic scar formation by targeting activin receptor-like kinase 5","volume":"852","author":"Ye","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1080\/09546634.2019.1704679","article-title":"Efficacy of fractional carbon dioxide laser therapy for burn scars: A meta-analysis","volume":"32","author":"Zhang","year":"2021","journal-title":"J. Dermatol. Treat."},{"key":"B102","doi-asserted-by":"publisher","first-page":"e16263","DOI":"10.1097\/md.0000000000016263","article-title":"Effect of pressure therapy for treatment of hypertrophic scar","volume":"98","author":"Zhang","year":"2019","journal-title":"Med. Baltim."},{"key":"B103","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1016\/j.burns.2013.10.012","article-title":"Amentoflavone inhibits angiogenesis of endothelial cells and stimulates apoptosis in hypertrophic scar fibroblasts","volume":"40","author":"Zhang","year":"2014","journal-title":"Burns"},{"key":"B104","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1080\/09546634.2017.1421309","article-title":"Identification of the potential targets for keloid and hypertrophic scar prevention","volume":"29","author":"Zhang","year":"2018","journal-title":"J. Dermatol. Treat."},{"key":"B105","doi-asserted-by":"publisher","first-page":"820817","DOI":"10.3389\/fmed.2022.820817","article-title":"Dramatic effect of botulinum toxin type A on hypertrophic scar: A promising therapeutic drug and its mechanism through the SP-NK1R pathway in cutaneous neurogenic inflammation","volume":"9","author":"Zhang","year":"2022","journal-title":"Front. Med."},{"key":"B106","doi-asserted-by":"publisher","first-page":"516","DOI":"10.3389\/fbioe.2020.00516","article-title":"Functional biomaterials for treatment of chronic wound","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/bjd.14108","article-title":"Baicalein attenuates hypertrophic scar formation via inhibition of the transforming growth factor-\u03b2\/Smad2\/3 signalling pathway","volume":"174","author":"Zhang","year":"","journal-title":"Br. J. Dermatol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s11010-015-2644-3","article-title":"Galangin inhibits hypertrophic scar formation via ALK5\/Smad2\/3 signaling pathway","volume":"413","author":"Zhang","year":"","journal-title":"Mol. Cell. Biochem."},{"key":"B109","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1111\/dsu.12474","article-title":"Dynamic hypoxia in scar tissue during human hypertrophic scar progression","volume":"40","author":"Zheng","year":"2014","journal-title":"Dermatol. Surg."},{"key":"B110","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.burns.2020.10.003","article-title":"Panax Notoginseng Saponins suppresses TRPM7 via the PI3K\/AKT pathway to inhibit hypertrophic scar formation in vitro","volume":"47","author":"Zhi","year":"2021","journal-title":"Burns."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1025602\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T06:45:57Z","timestamp":1665384357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.1025602\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":110,"alternative-id":["10.3389\/fphar.2022.1025602"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.1025602","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,10]]},"article-number":"1025602"}}