{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:11:55Z","timestamp":1793398315608,"version":"4.5.0"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006209","name":"Radboud Universitair Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Optimal healing of full\u2010thickness skin wounds remains a clinical challenge. While current skin substitutes aid burn wound management, there is still a need to effectively minimize scarring. Therefore, we developed type I collagen scaffolds with covalently bound ReGeneraTing Agent (RGTA) OTR4120 (OTR), a synthetic heparan sulphate analogue resistant to glycanase degradation (Col I\u2009+\u2009OTR). To further stimulate skin regeneration, collagen scaffolds with and without OTR4120 were subsequently loaded with sonic hedgehog (SHH), a key effector molecule in embryogenesis. The presence of OTR4120 and SHH in scaffolds was biochemically and histologically confirmed after crosslinking and sterilization. SHH was found deeper into collagen scaffolds in the presence of OTR4120. Addition of SHH to scaffolds showed lower expression of M1\u2010like cell surface markers, while Col I\u2009+\u2009OTR significantly enhanced IL\u201010 production. The potential of OTR4120 in wound healing was further evaluated in\u00a0vivo using a rat full\u2010thickness wound model over 28\u2009days. By day 14, macroscopic images revealed that OTR\u2010treated wounds better maintained the original wound shape. Histological analysis showed increased blood vessel formation, fewer scaffold remnants and more contiguous sebaceous glands in the granulation tissue with Col I\u2009+\u2009OTR scaffolds. This study demonstrates that OTR4120 could be a promising addition to acellular skin substitutes for improving acute wound healing.<\/jats:p>","DOI":"10.1111\/wrr.70096","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:46:47Z","timestamp":1759906007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Potential of Heparan Sulphate Mimetics Integrated Into Collagen Scaffolds for Enhanced Skin Wound Healing"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5689-9957","authenticated-orcid":false,"given":"Nancy","family":"Avila\u2010Martinez","sequence":"first","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-8856","authenticated-orcid":false,"given":"Roman","family":"Krymchenko","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6998-8008","authenticated-orcid":false,"given":"Merel","family":"Gansevoort","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7468-476X","authenticated-orcid":false,"given":"Maren","family":"Pfirrmann","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Aparicio","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-0282","authenticated-orcid":false,"given":"Agnes","family":"Choppin","sequence":"additional","affiliation":[{"name":"OTR3  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-1241","authenticated-orcid":false,"given":"Franck","family":"Chiappini","sequence":"additional","affiliation":[{"name":"OTR3  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-8717","authenticated-orcid":false,"given":"Denis","family":"Barritault","sequence":"additional","affiliation":[{"name":"OTR3  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-3528","authenticated-orcid":false,"given":"Martijn","family":"Verdoes","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"},{"name":"LUMC, Department of Immunology  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-6783","authenticated-orcid":false,"given":"Toin H.","family":"van Kuppevelt","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-6982","authenticated-orcid":false,"given":"Bouke K. H. L.","family":"Boekema","sequence":"additional","affiliation":[{"name":"Alliance of Dutch Burn Care Burn Research Lab  Beverwijk the Netherlands"},{"name":"Department of Plastic, Reconstructive and Hand Surgery AUMC  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3155-3030","authenticated-orcid":false,"given":"Willeke F.","family":"Daamen","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Research Institute for Medical Innovation Department of Medical BioSciences  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"StatPearls","author":"Schaefer T. J.","year":"2023"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a023267"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/bcr.0000000000000368"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmu.2015.07.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181d62b08"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.13226"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.18293.1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpaic.2021.10.023"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12121222"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0910536"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115199"},{"key":"e_1_2_8_13_1","volume-title":"Physiology, Granulation Tissue StatPearls","author":"Alhajj M.","year":"2022"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536\u2010021\u201000149\u20109"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228790"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtv.2009.11.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2010.10.011"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2019.0234"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/11.6.91R"},{"key":"e_1_2_8_20_1","first-page":"69","volume-title":"Tissue Regeneration \u2013 From Basic Biology to Clinical Application","author":"Neck J.","year":"2012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.09.043"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719\u2010016\u20109744\u20105"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10245947"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/jdb5040012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10123099"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1725"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310097110"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536\u2010021\u201000196\u20102"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb16020051"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0142\u20109612(98)00240\u20103"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma048485p"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym15091981"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010020\u201000304\u2010z"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719\u2010020\u201009925\u2010z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.102239"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wndm.2020.100180"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856\u2010018\u20106056\u20102"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10561\u2010024\u201010135\u20102"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.2112.12037"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jdb4040035"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46756"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010024\u201001692\u2010w"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkac057"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00636"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098228"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524\u2010475X.2011.00667.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2018.0828"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3bm00835e"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9ra06651a"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2ib00149g"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1028410"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970\u20100358.70724"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.03.068"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201015830\u20107"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1159\/000454919"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504492200"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719\u2010017\u20109773\u20108"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.572511"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12346"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.70096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:48:44Z","timestamp":1762609724000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.70096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":58,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/wrr.70096"],"URL":"https:\/\/doi.org\/10.1111\/wrr.70096","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70096"}}