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Besides modulation of the cell microenvironment, encapsulation of mammalian cells within hydrogel microbeads attract attention for cytoprotection through physical isolation of the encapsulated cells. The hydrogel formulations used for cell microencapsulation are largely dominated by ionically crosslinked alginate (Alg), which suffer from low structural stability under physiological culture conditions and poor cell\u2013matrix interactions. Here the fabrication of Alg templated silk and silk\/gelatin composite hydrogel microspheres with permanent or on\u2010demand cleavable enzymatic crosslinks using simple and cost\u2010effective centrifugation\u2010based droplet processing are demonstrated. The composite microbeads display structural stability under ion exchange conditions with improved mechanical properties compared to ionically crosslinked Alg microspheres. Human mesenchymal stem and neural progenitor cells are successfully encapsulated in the composite beads and protected against environmental factors, including exposure to polycations, extracellular acidosis, apoptotic cytokines, ultraviolet (UV) irradiation, anoikis, immune recognition, and particularly mechanical stress. The microbeads preserve viability, growth, and differentiation of encapsulated stem and progenitor cells after extrusion in viscous polyethylene oxide solution through a 27\u2010gauge fine needle, suggesting potential applications in injection\u2010based delivery and three\u2010dimensional bioprinting of mammalian cells with higher success rates.<\/jats:p>","DOI":"10.1002\/adhm.202200293","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T09:04:41Z","timestamp":1654851881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Cytoprotection of Human Progenitor and Stem Cells through Encapsulation in Alginate Templated, Dual Crosslinked Silk and Silk\u2013Gelatin Composite Hydrogel Microbeads"],"prefix":"10.1002","volume":"11","author":[{"given":"Onur","family":"Hasturk","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Tufts University  4 Colby Street 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