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In the current autologous cell\u2010based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)\u2010Cas9 knockout of TGF\u2010<jats:italic>\u03b2<\/jats:italic>\u2010activated kinase 1 (<jats:italic>TAK1<\/jats:italic>) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro\u2010inflammatory and catabolic NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway. The <jats:italic>TAK1<\/jats:italic>\u2010KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro\u2010inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the <jats:italic>TAK1<\/jats:italic>\u2010KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm\u2010shift for the creation of more potent and functional tissues for use in regenerative medicine.<\/jats:p>","DOI":"10.1002\/adhm.202202271","type":"journal-article","created":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T01:04:05Z","timestamp":1677373445000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Engineering Inflammation\u2010Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-2483","authenticated-orcid":false,"given":"Angela","family":"Bonato","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology ETH Z\u00fcrich  Z\u00fcrich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4384-6682","authenticated-orcid":false,"given":"Philipp","family":"Fisch","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology ETH Z\u00fcrich  Z\u00fcrich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Ponta","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology ETH Z\u00fcrich  Z\u00fcrich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fercher","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology ETH Z\u00fcrich  Z\u00fcrich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9681-8821","authenticated-orcid":false,"given":"Mikko","family":"Manninen","sequence":"additional","affiliation":[{"name":"Orton Orthopedic Hospital Helsinki  Helsinki 00280 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weber","sequence":"additional","affiliation":[{"name":"Division of Hand Surgery University Children's Hospital  Z\u00fcrich 8032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari K.","family":"Eklund","sequence":"additional","affiliation":[{"name":"Orton Orthopedic Hospital Helsinki  Helsinki 00280 Finland"},{"name":"Department of Rheumatology University of Helsinki and Helsinki University Hospital  Helsinki 00014 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4444-9208","authenticated-orcid":false,"given":"Goncalo","family":"Barreto","sequence":"additional","affiliation":[{"name":"Orton Orthopedic Hospital Helsinki  Helsinki 00280 Finland"},{"name":"Translational Immunology Research Program Faculty of Medicine University of Helsinki  Helsinki 00014 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-9909","authenticated-orcid":false,"given":"Marcy","family":"Zenobi\u2010Wong","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology ETH Z\u00fcrich  Z\u00fcrich 8093 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0498-0"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2016-000279"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.08.007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.blo.0000131233.83640.91"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-018-5321-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/2325967117S00186"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/JSA.0000000000000137"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-020-01515-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta21060"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2001.0482"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40575-w"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546510361950"},{"key":"e_1_2_8_13_1","first-page":"183","volume":"6","author":"Mortazavi F.","year":"2017","journal-title":"World J. 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