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However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer\u2010by\u2010layer self\u2010assembly, in which interleukin\u20104 (IL\u20104) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self\u2010assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL\u20104 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk\u2010based microcapsule delivery system can also provide strategies for the treatment of other diseases.<\/jats:p>","DOI":"10.1002\/smll.202302799","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T08:42:27Z","timestamp":1685695347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Self\u2010Assemble Silk Fibroin Microcapsules for Cartilage Regeneration through Gene Delivery and Immune Regulation"],"prefix":"10.1002","volume":"19","author":[{"given":"Shuangjian","family":"He","sequence":"first","affiliation":[{"name":"Department of orthopedics Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine Research Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of orthopedics Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of orthopedics Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of orthopedics Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine Research Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"An","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine Research Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-6899","authenticated-orcid":false,"given":"Tingting","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine Research Suzhou Hospital Affiliated Hospital of Medical School Nanjing University  Suzhou 215000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.72"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000479"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4324"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4085\/1062-6050-51.5.08"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082282"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1941738109350438"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.10.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-019-0840-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3139"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179208"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120375"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0385-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113324"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00487-6"},{"key":"e_1_2_9_15_1","first-page":"264","volume":"20","author":"Crunkhorn S.","year":"2021","journal-title":"Nat. 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