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Although stem cell therapy offers regenerative potential, its efficacy is restricted by poor survival and engraftment at the injury site. To address this, collagen microgels (CMGs) are developed to assemble with cells to form CMG\u2010based cellular microtissues (CCMs) with enhanced porosity, mass transfer, and viability. However, the diabetic microenvironment impairs healing by suppressing angiogenesis, keratinocyte migration, and fibroblast proliferation. Transcriptomic profiling identifies interleukin\u20108 (IL\u20108) as a key factor with multifaceted roles in promoting angiogenesis, migration, and proliferation. Compared with conventional aggregates, CCMs enhance adhesion, prevent anoikis, improve survival, and upregulate IL\u20108 via FGFR\u2010integrin\u2010ERK signaling. Functional studies using shRNA knockdown and adenoviral overexpression validate the therapeutic role of IL\u20108. In vitro co\u2010culture with keratinocytes, fibroblasts, and endothelial cells shows that CCMs promoted migration, proliferation, and angiogenesis\u2013effects diminished by IL\u20108 knockdown and amplified by overexpression. In a rat DFU model, CCMs accelerate wound closure by enhancing granulation tissue formation, collagen deposition, and expression of proliferative and angiogenic markers, all modulated by IL\u20108. These findings establish CCMs as an effective therapeutic platform for DFUs and highlight IL\u20108 overexpression as a strategy to further potentiate regeneration.<\/jats:p>","DOI":"10.1002\/smll.202511027","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:35:07Z","timestamp":1764156907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interleukin\u20108 Overexpressing Collagen Microgel\u2010Based Cellular Microtissue Accelerates the Healing of Diabetic Foot Ulcers"],"prefix":"10.1002","volume":"22","author":[{"given":"Haeun","family":"Chung","sequence":"first","affiliation":[{"name":"Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology KIST School Korea University of Science and Technology (UST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Young","family":"Jang","sequence":"additional","affiliation":[{"name":"Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Kyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-8218","authenticated-orcid":false,"given":"Sang\u2010Heon","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Biomaterials Biomedical Research Institute Korea Institute of Science and Technology (KIST)  Seoul 02792 Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology KIST School Korea University of Science and Technology (UST)  Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.32996\/bjns.2024.4.2.10"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-07144-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2024.113345"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108615"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13569"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2025.106852"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics8040193"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1427205"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071507"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0412-2"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-0938-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.2036"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.291"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.supmat.2021.100006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.07.020"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.12.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1216321"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v14.i4.364"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054290"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2016.08.060"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2000.5892"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13671-018-0234-9"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.03.035"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-018-0100-6"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1215\/S1152851704001061"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/5.12.1135"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2025.100615"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00159-7"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.304972"},{"key":"e_1_2_10_30_1","first-page":"20","volume":"1","author":"Mori S.","year":"2013","journal-title":"Med. 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