{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:53:23Z","timestamp":1790610803152,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31470968"],"award-info":[{"award-number":["31470968"]}]},{"name":"National Natural Science Foundation of China","award":["32101068"],"award-info":[{"award-number":["32101068"]}]},{"name":"National Natural Science Foundation of China","award":["2020YFA0710700"],"award-info":[{"award-number":["2020YFA0710700"]}]},{"name":"Nanjing Overseas Students Merit-Based Program Funding","award":["31470968"],"award-info":[{"award-number":["31470968"]}]},{"name":"Nanjing Overseas Students Merit-Based Program Funding","award":["32101068"],"award-info":[{"award-number":["32101068"]}]},{"name":"Nanjing Overseas Students Merit-Based Program Funding","award":["2020YFA0710700"],"award-info":[{"award-number":["2020YFA0710700"]}]},{"name":"National Key R&amp;D Program of Nanotechnology of China","award":["31470968"],"award-info":[{"award-number":["31470968"]}]},{"name":"National Key R&amp;D Program of Nanotechnology of China","award":["32101068"],"award-info":[{"award-number":["32101068"]}]},{"name":"National Key R&amp;D Program of Nanotechnology of China","award":["2020YFA0710700"],"award-info":[{"award-number":["2020YFA0710700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sensitive skin is defined as skin with low tolerance and high reactivity. Natural products, such as paeoniflorin and madecassoside, have unique skin care functionality. However, because they are hampered by the skin barrier, paeoniflorin and madecassoside have difficulty penetrating the stratum corneum, resulting in weakened skin barrier repair and anti-inflammatory effects. In addition, there is a lack of detailed studies on the efficacy of paeonol and madecassic in human skin, especially in 3D skin models and clinical trials. To overcome the low transdermal delivery issue, we developed nanoemulsions (PM-NEs) loaded with paeonol and madecassoside to improve their delivery efficiency and promote sensitive skin repair and anti-inflammation effects. Furthermore, systematic evaluations of the efficacy in cell line models, 3D skin models, and clinical trials were conducted. The PM-NEs effectively improved the efficacy of paeonol and madecassoside glucoside transdermal penetration and retention and enhanced cellular uptake. Cellular assays and 3D epidermal models showed that the PM-NEs significantly promoted the secretion of filamentous protein, aquaporin 3, Claudin-1, and hyaluronic acid, and considerably inhibited the secretion of interleukin 1\u03b1, interleukin 6, tumor necrosis factor-\u03b1, and prostaglandin E2 compared to free components. Notably, clinical trial data showed that the PM-NEs significantly reduced transepidermal water loss, a* values, erythropoietin, the amount of non-inflammatory acne, and the amount of inflammatory acne in the facial skin. Three levels of systematic studies suggest that co-delivery of paeoniflorin and madecassoside via nanoemulsions is a promising strategy to improve topical delivery efficiency and anti-inflammatory repair efficacy in sensitive skin.<\/jats:p>","DOI":"10.3390\/molecules28135275","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:54:23Z","timestamp":1688950463000},"page":"5275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Systematic Study of Paeonol\/Madecassoside Co-Delivery Nanoemulsion Transdermal Delivery System for Enhancing Barrier Repair and Anti-Inflammatory Efficacy"],"prefix":"10.3390","volume":"28","author":[{"given":"Wangwang","family":"Lu","sequence":"first","affiliation":[{"name":"Guangzhou Jiyan Cosmetics Technology Co., Ltd., Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0451-591X","authenticated-orcid":false,"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Jiyan Cosmetics Technology Co., Ltd., Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Biomaterials, Tech Institute for Advanced Materials, College of Materials Science and Engineering, Suqian Advanced Materials Industry Technology Innovation Center, NJTech-BARTY Joint Research Center for Innovative Medical Technology, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"},{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100117","DOI":"10.1016\/j.prmcm.2022.100117","article-title":"Anti-allergic activity of natural plant products for the treatment of sensitive skin: A review","volume":"3","author":"Guo","year":"2022","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/ics.12559","article-title":"Clinical and in vitro evaluation of new anti-redness cosmetic products in subjects with winter xerosis and sensitive skin","volume":"41","author":"Nisbet","year":"2019","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/j.1468-3083.2012.04648.x","article-title":"Self-declared sensitive skin in China: A community-based study in three top metropolises","volume":"27","author":"Xu","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1468-3083.2006.01455.x","article-title":"Self-reported skin sensitivity in a general adult population in France: Data of the SU.VI.MAX cohort","volume":"20","author":"Guinot","year":"2006","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e521","DOI":"10.1111\/j.1365-2230.2009.03487.x","article-title":"How do perceptions of sensitive skin differ at different anatomical sites? An epidemiological study","volume":"34","author":"Farage","year":"2009","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/ics.12283","article-title":"Brief analysis of causes of sensitive skin and advances in evaluation of anti-allergic activity of cosmetic products","volume":"38","author":"Fan","year":"2016","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/ics.12817","article-title":"Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements","volume":"45","author":"Borghi","year":"2023","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1600-0625.2009.00861.x","article-title":"Putative neuronal mechanisms of sensitive skin","volume":"18","author":"Schneider","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2147\/CCID.S313429","article-title":"Current advances of nanocarrier technology-based active cosmetic ingredients for beauty applications","volume":"14","author":"Zhou","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"896874","DOI":"10.3389\/fimmu.2022.896874","article-title":"Paeonol Interferes With Quorum-Sensing in pseudomonas aeruginosa and modulates inflammatory responses in vitro and in vivo","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.intimp.2019.04.033","article-title":"Paeonol: Pharmacological effects and mechanisms of action","volume":"72","author":"Zhang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vellasamy, S., Murugan, D., Abas, R., Alias, A., Seng, W.Y., and Woon, C.K. (2021). Biological Activities of paeonol in cardiovascular diseases: A review. Molecules, 26.","DOI":"10.3390\/molecules26164976"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1098617","DOI":"10.1155\/2018\/1098617","article-title":"Beneficial effects exerted by paeonol in the management of atherosclerosis","volume":"2018","author":"Lu","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2723","DOI":"10.1038\/cddis.2017.150","article-title":"Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPAR\u03b3\/AMPK\/ACC1 pathway","volume":"8","author":"Xu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.2147\/DDDT.S383632","article-title":"Madecassic acid ameliorates the progression of osteoarthritis: An in vitro and in vivo study","volume":"16","author":"Fu","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5462633","DOI":"10.1155\/2021\/5462633","article-title":"Pharmacological effects of centella asiatica on skin diseases: Evidence and possible mechanisms","volume":"2021","author":"Park","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112440","DOI":"10.1016\/j.colsurfb.2022.112440","article-title":"Emerging trends of nanotechnology in advanced cosmetics","volume":"214","author":"Dubey","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s13346-017-0390-7","article-title":"Emulsion versus nanoemulsion: How much is the formulative shift critical for a cosmetic product?","volume":"8","author":"Musazzi","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6178","DOI":"10.1021\/acsnano.8b07961","article-title":"Non-Lamellar lyotropic liquid crystallinelipid nanoparticles for the next generation of nanomedicine","volume":"13","author":"Zhai","year":"2019","journal-title":"ACS Nano"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.smaim.2022.03.001","article-title":"Liquid crystalline lipid nanoparticles for combined delivery of curcumin, fish oil and BDNF: In vitro neuroprotective potential in a cellular model of tunicamycin-induced endoplasmic reticulum stress","volume":"3","author":"Miora","year":"2022","journal-title":"Smart Mater. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, B., Lei, M., Huang, W., Liu, G., Jiang, F., Peng, D., Huang, Q., and Jin, W. (2021). Improved storage properties and cellular uptake of casticin-loaded nanoemulsions stabilized by whey protein-lactose conjugate. Foods, 10.","DOI":"10.3390\/foods10071640"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1208\/s12249-014-0129-4","article-title":"Nanoemulsion for solubilization, stabilization, and in vitro release of pterostilbene for oral delivery","volume":"15","author":"Zhang","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, B.H., and Stephen Inbaraj, B. (2019). Nanoemulsion and nanoliposome based strategies for improving anthocyanin stability and bioavailability. Nutrients, 11.","DOI":"10.3390\/nu11051052"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Abd, E., Benson, H.A.E., Roberts, M.S., and Grice, J.E. (2018). Minoxidil skin delivery from nanoemulsion formulations containing eucalyptol or oleic acid: Enhanced diffusivity and follicular targeting. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10010019"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jconrel.2022.09.035","article-title":"Nanoemulsion applications in photodynamic therapy","volume":"351","author":"Moghassemi","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102685","DOI":"10.1016\/j.cis.2022.102685","article-title":"Recent developments in industrial applications of nanoemulsions","volume":"304","author":"Ozogul","year":"2022","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8281","DOI":"10.1016\/j.biomaterials.2011.07.032","article-title":"Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles","volume":"32","author":"Wang","year":"2011","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pangeni, R., Panthi, V.K., Yoon, I.S., and Park, J.W. (2018). Preparation, characterization, and in vivo evaluation of an oral multiple nanoemulsive system for co-delivery of pemetrexed and quercetin. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030158"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1166\/jbn.2021.3202","article-title":"A Nanocrystals-Based Topical Drug Delivery System with Improved Dermal Penetration and Enhanced Treatment of Skin Diseases","volume":"17","author":"Sun","year":"2021","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/03639045.2017.1391836","article-title":"Optimization of nutraceutical coenzyme Q10 nanoemulsion with improved skin permeability and anti-wrinkle efficiency","volume":"44","author":"Makky","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s00403-019-01964-3","article-title":"Resveratrol-loaded nanoemulsion gel system to ameliorate UV-induced oxidative skin damage: From in vitro to in vivo investigation of antioxidant activity enhancement","volume":"311","author":"Sharma","year":"2019","journal-title":"Arch. Dermatol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101693","DOI":"10.1016\/j.jddst.2020.101693","article-title":"Nanoliposomes codelivering bioactive peptides produce enhanced anti-aging effect in human skin","volume":"57","author":"Han","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.msec.2018.06.049","article-title":"Formulation characterization and in vitro drug release of hydrogel-thickened nanoemulsions for topical delivery of 8-methoxypsoralen","volume":"92","author":"Barradas","year":"2018","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Suresh, P., Salem-Bekhit, M.M., Veedu, H.P., Alshehri, S., Nair, S.C., Bukhari, S.I., Viswanad, V., Taha, E.I., Sahu, R.K., and Ghoneim, M.M. (2022). Development of a novel methotrexate-loaded nanoemulsion for rheumatoid arthritis treatment with site-specific targeting subcutaneous delivery. Nanomaterials, 12.","DOI":"10.3390\/nano12081299"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3109\/03639045.2011.650648","article-title":"Preparation of Coenzyme Q10 nanostructured lipid carriers for epidermal targeting with high-pressure microfluidics technique","volume":"39","author":"Chen","year":"2013","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"646554","DOI":"10.3389\/fbioe.2021.646554","article-title":"Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: Novel strategies for effective transdermal applications","volume":"9","author":"Yu","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2001051","DOI":"10.1002\/cbdv.202001051","article-title":"Positive promoting effects of smilax china flower absolute on the wound healing\/skin barrier repair-related responses of HaCaT human skin keratinocytes","volume":"18","author":"Li","year":"2021","journal-title":"Chem. Biodivers."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Xu, R., Ma, L., Chen, T., and Wang, J. (2022). Sophorolipid Suppresses LPS-Induced Inflammation in RAW264.7 Cells through the NF-\u03baB Signaling Pathway. Molecules, 27.","DOI":"10.3390\/molecules27155037"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120887","DOI":"10.1016\/j.lfs.2022.120887","article-title":"Brassinosteroids control the inflammation, oxidative stress and cell migration through the control of mitochondrial function on skin regeneration","volume":"307","author":"Xiong","year":"2022","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"183826","DOI":"10.1016\/j.bbamem.2021.183826","article-title":"Emerging roles for AQP in mammalian extracellular vesicles","volume":"1864","author":"Bill","year":"2022","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"C1144","DOI":"10.1152\/ajpcell.00075.2020","article-title":"Aquaporin-3 in the epidermis: More than skin deep","volume":"318","author":"Bollag","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"AB218","DOI":"10.1016\/j.jaad.2020.06.959","article-title":"18672 Evaluation of skin barrier and hydration effects of a new rebalancing moisturizing treatment cream in a human epidermal skin model","volume":"83","author":"Nelson","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/j.1365-2133.2009.09342.x","article-title":"Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: Evaluation of minimally invasive methods","volume":"161","author":"Kezic","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e145185","DOI":"10.1172\/jci.insight.145185","article-title":"Particulate matter causes skin barrier dysfunction","volume":"6","author":"Kim","year":"2021","journal-title":"JCI Insight"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jconrel.2016.08.007","article-title":"The role of tight junctions in skin barrier function and dermal absorption","volume":"242","author":"Bergmann","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/nyas.13367","article-title":"Transcriptional mechanisms coordinating tight junction assembly during epithelial differentiation","volume":"1397","author":"Boivin","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1091\/mbc.E15-04-0232","article-title":"A complex of ZO-1 and the BAR-domain protein TOCA-1 regulates actin assembly at the tight junction","volume":"26","author":"Tietgens","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1055\/a-0991-7585","article-title":"The Potential applications of hyaluronic acid hydrogels in biomedicine","volume":"70","author":"Ahmadian","year":"2020","journal-title":"Drug Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.copbio.2016.02.008","article-title":"Recent advances in hyaluronic acid hydrogels for biomedical applications","volume":"40","author":"Highley","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.carbpol.2011.03.019","article-title":"Chemical modifications of hyaluronic acid for the synthesis of derivatives for a broad range of biomedical applications","volume":"85","author":"Zuber","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/exd.13531","article-title":"3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function","volume":"27","author":"Niehues","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41540-020-00160-8","article-title":"Assessment of skin barrier function using skin images with topological data analysis","volume":"6","author":"Koseki","year":"2020","journal-title":"NPJ Syst. Biol. Appl."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhou, H., Tan, X., Chen, G., Liu, X., Feng, A., Liu, Z., and Liu, W. (2023). Extracellular vesicles of commensal skin microbiota alleviate cutaneous inflammation in atopic dermatitis mouse model by reestablishing skin homeostasis. J. Investig. Dermatol.","DOI":"10.1016\/j.jid.2023.02.023"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e00251","DOI":"10.1016\/j.bprint.2022.e00251","article-title":"Bioprinted and manual human epidermis production: A compared performance for skin irritation tests","volume":"29","author":"Bagatin","year":"2023","journal-title":"Bioprinting"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:08:07Z","timestamp":1760126887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,7]]},"references-count":54,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28135275"],"URL":"https:\/\/doi.org\/10.3390\/molecules28135275","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,7]]}}}