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Bio\u2010orthogonal chemistries have been developed that do not react with biologically relevant functional groups, thereby preventing these undesirable side reactions. However, previously developed biomaterials using these chemistries still possess less than ideal properties for cell encapsulation, such as slow gelation kinetics and limited tuning of matrix mechanics and biochemistry. Here, engineered elastin\u2010like proteins (ELPs) are developed that crosslink via strain\u2010promoted azide\u2010alkyne cycloaddition (SPAAC) or Staudinger ligation. The SPAAC\u2010crosslinked materials form gels within seconds and complete gelation within minutes. These hydrogels support the encapsulation and phenotypic maintenance of human mesenchymal stem cells, human umbilical vein endothelial cells, and murine neural progenitor cells. SPAAC\u2010ELP gels exhibit independent tuning of stiffness and cell adhesion, with significantly improved cell viability and spreading observed in materials containing a fibronectin\u2010derived arginine\u2010glycine\u2010aspartic acid (RGD) domain. The crosslinking chemistry used permits further material functionalization, even in the presence of cells and serum. These hydrogels are anticipated to be useful in a wide range of applications, including therapeutic cell delivery and bioprinting.<\/jats:p>","DOI":"10.1002\/adfm.201505329","type":"journal-article","created":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T04:29:28Z","timestamp":1458534568000},"page":"3612-3620","source":"Crossref","is-referenced-by-count":149,"title":["Bio\u2010Orthogonally Crosslinked, Engineered Protein Hydrogels with Tunable Mechanics and Biochemistry for Cell Encapsulation"],"prefix":"10.1002","volume":"26","author":[{"given":"Christopher M.","family":"Madl","sequence":"first","affiliation":[{"name":"Department of Bioengineering Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily M.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering Stanford University  Stanford CA 94305 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