Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues

Mian Wang¹, Wanlu Li¹, Jin Hao², Ling Cai¹, Xuan Mei¹, Regina Sanchez Flores¹, Penélope Cerón Castillo¹, Carlos Ezio Garciamendez-Mijares¹, Xuan Mu¹, Xiao Kuang¹, Xianbin Yu³, Jugal Kishore Sahoo⁴, Guosheng Tang¹, Zeyu Luo¹, Guillermo Wells¹, Zhongmin Liu⁵, Alfredo Quiñones-Hinojosa⁶, Kevin Eggan², Shaorong Gao⁷, Yu Shrike Zhang⁸

Affiliations

¹ Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
² Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
⁴ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
⁵ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Departments of Neurosurgery, Oncology, and Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
⁷ Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁸ Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: yszhang@bwh.harvard.edu.

PMID: 41365296
DOI: 10.1016/j.cell.2025.11.012

Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues

Mian Wang et al. Cell. 2026.

. 2026 Jan 8;189(1):106-122.e26.

doi: 10.1016/j.cell.2025.11.012. Epub 2025 Dec 8.

Authors

Affiliations

¹ Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.
² Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
⁴ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
⁵ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Departments of Neurosurgery, Oncology, and Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
⁷ Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁸ Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: yszhang@bwh.harvard.edu.

PMID: 41365296
DOI: 10.1016/j.cell.2025.11.012

Abstract

Conventional hydrogel-based bioprinting methods often suffer from insufficient cell densities, which may limit crucial cell-cell interactions and impair overall tissue functions. Here, we present an approach that modifies cell membranes with acrylate bonds, allowing living cells at physiological densities (up to ∼10⁹ cells mL^-1) to serve directly as bioinks, demonstrating photoactivated bioprinting through digital light processing using purely cellular bioinks. Our cell-dense bioinks (CLINKs) rapidly produce tissue constructs that closely mimic native tissues, characterized by strong structural relevancy and robust functionality. The high cellularity and living nature of CLINKs enable the creation of advanced biological models such as connected neural circuits and rhythmically contracting mini-hearts derived entirely from stem cells, effectively capturing essential native-like behaviors. Implants created through this method showcase the capacity to integrate with the host, thereby promoting regeneration. Our CLINK technology holds substantial promise in tissue biofabrication, opening alternative avenues for biomedical applications.

Keywords: 3D bioprinting; cardiac tissues; cardiomyocytes; cell-dense; digital light processing; liver tissues; neural cells; neural circuits; scaffold-free; skin regeneration.

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Conflict of interest statement

Declaration of interests Y.S.Z. consulted for Allevi by 3D Systems; co-founded, consults for, and holds options of Linton Lifesciences; and sits on the scientific advisory board and holds options of Xellar Biosystems. The relevant interests are managed by the Brigham and Women’s Hospital.

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Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues

Affiliations

Biomaterial-minimalistic photoactivated bioprinting of cell-dense tissues

Authors

Affiliations

Abstract

Conflict of interest statement

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