Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues

Mian Wang, Wanlu Li, Jin Hao, Arthur Gonzales, Zhibo Zhao, Regina Sanchez Flores, Xiao Kuang, Xuan Mu, Terry Ching, Guosheng Tang, Zeyu Luo, Carlos Ezio Garciamendez-Mijares, Jugal Kishore Sahoo, Michael F. Wells, Gengle Niu, Prajwal Agrawal, Alfredo Quiñones-Hinojosa, Kevin Eggan and Yu Shrike Zhang ()
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Mian Wang: Brigham and Women’s Hospital, Harvard Medical School
Wanlu Li: Brigham and Women’s Hospital, Harvard Medical School
Jin Hao: Harvard University
Arthur Gonzales: University of the Philippines Diliman
Zhibo Zhao: Brigham and Women’s Hospital, Harvard Medical School
Regina Sanchez Flores: Brigham and Women’s Hospital, Harvard Medical School
Xiao Kuang: Brigham and Women’s Hospital, Harvard Medical School
Xuan Mu: Brigham and Women’s Hospital, Harvard Medical School
Terry Ching: Brigham and Women’s Hospital, Harvard Medical School
Guosheng Tang: Brigham and Women’s Hospital, Harvard Medical School
Zeyu Luo: Brigham and Women’s Hospital, Harvard Medical School
Carlos Ezio Garciamendez-Mijares: Brigham and Women’s Hospital, Harvard Medical School
Jugal Kishore Sahoo: Tufts University
Michael F. Wells: Harvard University
Gengle Niu: Harvard University
Prajwal Agrawal: Brigham and Women’s Hospital, Harvard Medical School
Alfredo Quiñones-Hinojosa: Mayo Clinic
Kevin Eggan: Harvard University
Yu Shrike Zhang: Brigham and Women’s Hospital, Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed with gelatin methacryloyl to achieve high-performance bioprinting, followed by selectively enzymatic digestion of HAMA, resulting in tissue-matching mechanical properties without losing the structural complexity and fidelity. Our method allows cellular morphological and functional improvements across multiple bioprinted tissue types featuring a wide range of mechanical stiffness, from the muscles to the brain, the softest organ of the human body. This platform endows us to biofabricate mechanically precisely tunable constructs to meet the biological function requirements of target tissues, potentially paving the way for broad applications in tissue and tissue model engineering.

Date: 2022
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DOI: 10.1038/s41467-022-31002-2

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