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However, conventional photolabile hydrogels often have poor efficiency upon two\u2010photon excitation in the near\u2010infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high\u2010speed two\u2010photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin\u2010based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin\u2010functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi\u2010synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two\u2010photon irradiation at 780\u2005nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300\u2005mm\u2009s\n                    <jats:sup>\u22121<\/jats:sup>\n                    and low laser dosage down to 10\u2005mW. Further, we demonstrate fast two\u2010photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser\u2010guided tissue fabrication at high spatial resolution.\n                  <\/jats:p>","DOI":"10.1002\/anie.202404599","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T09:57:24Z","timestamp":1721296644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Coumarin\u2010Based Photodegradable Hydrogels Enable Two\u2010Photon Subtractive Biofabrication at 300\u2005mm\u2009s\n                    <sup>\u22121<\/sup>"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2461-638X","authenticated-orcid":false,"given":"Wanwan","family":"Qiu","sequence":"first","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich  Gloriastrasse 39 8092 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9954-8345","authenticated-orcid":false,"given":"Christian","family":"Gehre","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich  Gloriastrasse 39 8092 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime Pietrantuono","family":"Nepomuceno","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich  Gloriastrasse 39 8092 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5264-1211","authenticated-orcid":false,"given":"Yinyin","family":"Bao","sequence":"additional","affiliation":[{"name":"Institute for Chemical and Bioengineering, ETH Zurich  Vladimir-Prelog-Weg 1\u20135\/10 8093 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8436-9651","authenticated-orcid":false,"given":"Zhiquan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Materials and Energy Guangdong University of Technology  Guangzhou, Guangdong 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-7725","authenticated-orcid":false,"given":"Ralph","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich  Gloriastrasse 39 8092 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-3230","authenticated-orcid":false,"given":"Xiao\u2010Hua","family":"Qin","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich  Gloriastrasse 39 8092 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"e_1_2_3_1_1","unstructured":"\u00a0"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.71"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200704857"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw9021"},{"key":"e_1_2_3_5_1","unstructured":"\u00a0"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-022-00420-7"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2022.03.013"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3839"},{"key":"e_1_2_3_9_2","volume":"1","author":"Li J.","year":"2016","journal-title":"Nat. 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