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Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)\u20104 arm maleimide (PEG\u20104MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin\u201010, IL\u201010, and cross\u2010linked with a collagenase\u2010degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease\u2010relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL\u201010 incorporated in the hydrogel was optimized to be 500\u2009ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel\u2010incorporated DCs with lower IL\u201010 loading amounts. Additionally, the effect of the degradability of the PEG\u20104MAL hydrogel on the release rate of incorporated IL\u201010 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL\u201010 release rates. This IL\u201010\u2010conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.<\/jats:p>","DOI":"10.1002\/jbm.a.37714","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T06:50:23Z","timestamp":1712040623000},"page":"1317-1336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimization of <scp>Interleukin<\/scp>\u201010 incorporation for dendritic cells embedded in <scp>Poly(ethylene glycol)<\/scp> hydrogels"],"prefix":"10.1002","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6578-8555","authenticated-orcid":false,"given":"Fredrick","family":"Bulondo","sequence":"first","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology  Atlanta Georgia USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University  Atlanta Georgia USA"},{"name":"Department of Biomedical Sciences and Engineering Mbarara University of Science and Technology  Mbarara Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-9172","authenticated-orcid":false,"given":"Julia E.","family":"Babensee","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology  Atlanta Georgia USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston A","year":"2008","journal-title":"Lancet"},{"issue":"2","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1212\/01.wnl.0000316802.35974.34","article-title":"Temporal trends in the incidence of multiple sclerosis: a systematic review","volume":"71","author":"Alonso A","year":"2008","journal-title":"Neurology"},{"issue":"5","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1212\/01.wnl.0000252807.38124.a3","article-title":"How common are the \u201ccommon\u201d neurologic disorders?","volume":"68","author":"Hirtz D","year":"2007","journal-title":"Neurology"},{"issue":"8","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1136\/jnnp.2006.090365","article-title":"Costs and quality of life of patients with multiple sclerosis in Europe","volume":"77","author":"Kobelt G","year":"2006","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neuron.2006.09.011","article-title":"The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration","volume":"52","author":"Hauser SL","year":"2006","journal-title":"Neuron"},{"issue":"4","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1212\/WNL.0b013e3182270402","article-title":"Cost\u2010effectiveness of disease\u2010modifying therapy for multiple sclerosis: a population\u2010based study","volume":"77","author":"Noyes K","year":"2011","journal-title":"Neurology"},{"issue":"9350","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(02)12023-X","article-title":"Mitoxantrone in progressive multiple sclerosis: a placebo\u2010controlled, double\u2010blind, randomised, multicentre trial","volume":"360","author":"Hartung H\u2010P","year":"2002","journal-title":"Lancet"},{"issue":"9","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa044397","article-title":"A randomized, placebo\u2010controlled trial of natalizumab for relapsing multiple sclerosis","volume":"354","author":"Polman CH","year":"2006","journal-title":"N Engl J Med"},{"issue":"3","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1212\/WNL.50.3.701","article-title":"Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. 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