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Despite the development of various channel networks for large\u2010scale engineered tissue perfusion culture, achieving sufficiently dense, architecturally complex networks with microscale channels in large\u2010scale matrix has remained challenging. In this work, we introduce a design and fabrication strategy for creating intricate three\u2010dimensional microfluidic networks (3D MFNs) within centimeter\u2010scale cell\u2010laden hydrogels using sacrificial 3D\u2010assembled templates. A theoretical model was established to inversely design 3D MFNs with target architectures by optimizing the two\u2010dimensional (2D) geometries of precursor structures and applying compressive strains for mechanically\u2010guided 3D assembly. Multiple types of 3D MFNs were presented, including interconnected ribbons, ribbon\u2010film hybrids, and multilayer networks. In particular, a dendritic MFN template was embedded within a 1\u2010centimeter cell\u2010laden 12\u00a0wt.% GelMA hydrogel, where template dissolution yielded robust microchannels that enabled efficient nutrient transport and supported cell survival and differentiation in vitro. Moreover, when implanted in vivo, the dendritic MFN functioned as a passageway for nutrient delivery and endogenous cell migration into the hydrogel, significantly enhancing cell survival. This strategy provides a versatile platform for large\u2010scale 3D tissue culture and targeted tissue differentiation.<\/jats:p>","DOI":"10.1002\/smll.202512229","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:45:12Z","timestamp":1791971112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3D Microfluidic Networks Formed by Mechanically Guided Compressive Buckling for Large\u2010Scale Perfused Tissue Culture"],"prefix":"10.1002","author":[{"given":"Hongyun","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Materials Science and Engineering University of Science and Technology Beijing  Beijing People's Republic of China"},{"name":"Department of Prothodontics National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology NHC Key Laboratory of Digital Stomatology NMPA Key Laboratory for Dental Materials Peking University School and Hospital of Stomatology  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Applied Mechanics Laboratory Department of Engineering Mechanics Tsinghua University  Beijing People's Republic of China"},{"name":"Laboratory of Flexible Electronics Technology Tsinghua University  Beijing People's Republic of China"},{"name":"Department of Materials Science and Engineering National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiruo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Prothodontics National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Research Center of Oral Biomaterials and Digital Medical 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Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Engineering Research Center of Advanced Dental Technology and Materials Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangming","family":"Shen","sequence":"additional","affiliation":[{"name":"Applied Mechanics Laboratory Department of Engineering Mechanics Tsinghua University  Beijing People's Republic of China"},{"name":"Laboratory of Flexible Electronics Technology Tsinghua University  Beijing People's Republic of China"},{"name":"Department of Materials Science and Engineering National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering University of Science and Technology Beijing  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering University of Science and Technology Beijing  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzheng","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering University of Science and Technology Beijing  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Prothodontics National Center for Stomatology National Clinical Research Center for Oral Diseases National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology NHC Key Laboratory of Digital Stomatology NMPA Key Laboratory for Dental Materials Peking University School and Hospital of Stomatology  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering College of Future Technology Peking University  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Biomedical Analysis Tsinghua University  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Advanced Materials of Ministry of Education School of Materials Science and Engineering Tsinghua University  Beijing People's Republic of 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