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However, the ability to unravel how these cues dictate the biological function in bioprinted constructs is limited by the lack of extracellular matrix (ECM)\u2010mimetic bioinks with fully controllable properties. In this study, a multifunctional bioink that uniquely combines the independent control over the biochemical and biophysical cues that regulate cell fate with the bioorthogonal nature of thiol\u2013norbornene photoclick chemistry is designed for the extrusion bioprinting of bioinspired 3D cellular niches with tunable properties. The bioink rheology is controlled by ionic gelation, being dependent on both the type and content of divalent ions (calcium and barium), while the mechanical and biochemical properties of hydrogels are tailored via a post printing thiol\u2013ene reaction. Bioprinted cell\u2010adhesive and protease\u2010degradable hydrogels modulate cell proliferation and ECM deposition in a matrix\u2010stiffness dependent manner over 14 days of culture regardless of cell spreading, demonstrating the ability to probe the effect of matrix cues on cell response. This bioink can be used as a versatile platform where building blocks can be rationally combined for the bioprinting of functional cell\u2010 and tissue\u2010specific constructs with controlled cellular behavior.<\/jats:p>","DOI":"10.1002\/adhm.202001176","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T03:47:18Z","timestamp":1604288838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Bioprinting a Multifunctional Bioink to Engineer Clickable 3D Cellular Niches with Tunable Matrix Microenvironmental Cues"],"prefix":"10.1002","volume":"10","author":[{"given":"R\u00faben F.","family":"Pereira","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto Nacional de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar Universidade do Porto  Porto 4050\u2010313 Portugal"}]},{"given":"Bianca N.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto Nacional de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-726X","authenticated-orcid":false,"given":"Paulo J.","family":"B\u00e1rtolo","sequence":"additional","affiliation":[{"name":"School of Mechanical, Aerospace, and Civil Engineering University of Manchester  Manchester M13 9PL UK"},{"name":"Manchester Institute of Biotechnology University of Manchester  Manchester M1 7DN UK"}]},{"given":"Pedro L.","family":"Granja","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto 4200\u2010135 Portugal"},{"name":"INEB \u2013 Instituto Nacional de Engenharia Biom\u00e9dica Universidade do Porto  Porto 4200\u2010135 Portugal"}]}],"member":"311","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2017.10.015"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.10.076"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201604983"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9051"},{"key":"e_1_2_7_3_3","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201801331"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201906423"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201808750"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.07.030"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201700798"},{"key":"e_1_2_7_6_1","first-page":"356","author":"Zhang Y. 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