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Though injectable biomaterials offer protection against membrane\u2010damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and\/or chemically ill\u2010defined. This work presents a shear\u2010thinning and self\u2010healing telechelic recombinant protein\u2010based hydrogel designed around XTEN \u2013 a well\u2010expressible, non\u2010immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to \u201ceXTENd\u201d the in vivo half\u2010life of fused protein therapeutics. By flanking XTEN with self\u2010associating coil domains derived from cartilage oligomeric matrix protein, single\u2010component physically crosslinked hydrogels exhibiting rapid shear thinning and self\u2010healing through homopentameric coiled\u2010coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables\u00a0a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem\u2010cell\u2010derived cardiomyocytes (hESC\u2010CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN\u2010based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications.<\/jats:p>","DOI":"10.1002\/advs.202301708","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T06:56:12Z","timestamp":1710312972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetically Encoded XTEN\u2010based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2565-1267","authenticated-orcid":false,"given":"Jennifer I.","family":"Bennett","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering University of Washington  Seattle WA 98105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-6950","authenticated-orcid":false,"given":"Mary 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