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Although numerous pharmaceutical agents are currently available, their depigmentation effects are still not satisfactory. In this study, we investigated the effects of chitosan, a natural marine product, on melanin synthesis and melanosome transfer. Treating B16F10 melanoma cells caused the inhibitory effect of chitosan on melanogenesis to be more prominent under \u03b1\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010MSH) stimulation. Chitosan samples of different molecular weights inhibited melanogenesis to a comparable extent, whereas increasing the deacetylation of chitosan enhanced its depigmentation effects. Chitosan was found to effectively reduce basal or \u03b1\u2010MSH\u2010stimulated melanogenesis by suppressing the expression of melanogenic\u2010related proteins (microphthalmia transcription factor, tyrosinase, and tyrosinase\u2010related protein\u20101 and protein\u20102) as well as inhibiting tyrosinase activity. Moreover, the inhibitory effect of chitosan on melanogenesis in human melanocytes was confirmed. A transwell coculture system using permeable inserts was designed to allow the contact of human melanocytes and human HaCaT keratinocytes through the tiny holes on the membrane. When chitosan was added to this melanocyte\u2013keratinocyte coculture system, we observed decreased melanosome release from melanocytes. Reduced melanosome uptake by keratinocytes was also observed, and was probably mediated by inhibiting protease\u2010activated receptor 2 expression. Many skin\u2010whitening agents can modulate the process of melanogenesis, but few have been shown to inhibit the melanosome transfer and uptake process. We demonstrated that chitosan exhibits a robust effect on depigmentation by inhibiting melanogenesis as well as melanosome transfer and uptake. Therefore, chitosan represents a potential therapeutic agent for hyperpigmentation disorders.<\/jats:p>","DOI":"10.1002\/jbm.b.34472","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T09:32:45Z","timestamp":1566466365000},"page":"1239-1250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of melanin synthesis and melanosome transfer by chitosan biomaterials"],"prefix":"10.1002","volume":"108","author":[{"given":"Hsi\u2010Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Shuan","family":"Chou","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai\u2010Horng","family":"Young","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering College of Medicine and College of Engineering, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai\u2010Chen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Surgery National Taiwan University Hospital and College of Medicine  Taipei Taiwan"},{"name":"Research Center for Developmental Biology and Regenerative Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.413"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1473-2165.2007.00339.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1473-2165.2007.00295.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10062440"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2000.tb02201.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.01.060"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.11.049"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2000.39"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.748"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2001.140506.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10837450701212560"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2010.02.024"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020404615898"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12873289"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.07.012"},{"issue":"12","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1242\/jcs.114.12.2335","article-title":"Inhibition of melanogenesis in response to oxidative stress: Transient downregulation of melanocyte differentiation markers and possible involvement of microphthalmia transcription factor","volume":"114","author":"Jim\u00e9nez\u2010Cervantes C.","year":"2001","journal-title":"Journal of Cell Science"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules181215724"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09477.x"},{"issue":"4","key":"e_1_2_8_20_1","first-page":"257","article-title":"Formulation of chitosan patch incorporating Artocarpus altilis heartwood extract for improving hyperpigmentation","volume":"68","author":"Kwankaew J.","year":"2017","journal-title":"Journal of Cosmetic Science"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2002.5665"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2004.05.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(01)00068-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1967.187"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1467-2494.2003.00164.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.09.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/B978-0-12-398358-9.00020-3","volume-title":"Cell interactions with polymers. 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