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Harvard Medical School, 현 한국과학기술연구원

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Trends Biotechnol., Sep 20 2024, S0167-7799(24)00212-9 | https://doi.org/10.1016/j.tibtech.2024.08.001 Engineering large-scale hiPSC-derived vessel-integrated muscle-like lattices for enhanced volumetric muscle regeneration

Myung Chul Lee ^1,2,22, Yasamin A. Jodat ^1,22, Yori Endo³, Alejandra Rodríguez-delaRosa ^4,5,6, Ting Zhang ^1,7, Mehran Karvar ³, Ziad Al Tanoury ^4,5,6, Jacob Quint ^8,9, Tom Kamperman ¹, Kiavash Kiaee¹, Sofia Lara Ochoa ¹, Kun Shi ¹, Yike Huang ¹, Montserrat Pineda Rosales ¹, Adnan Arnaout ¹, Hyeseon Lee ¹, Jiseong Kim ¹, Eder Luna Ceron ¹, Isaac Garcia Reyes ¹, Adriana C. Panayi ³, Angel Flores Huidobro Martinez ¹, Xichi Wang ¹, Ki-Tae Kim ^10,11, Jae-I Moon ^10,11, Seung Gwa Park ^10,11, Kangju Lee¹², Michelle A. Calabrese ¹³, Shabir Hassan ^1,14,15, Junmin Lee ^1,16, Ali Tamayol ^8,9, Luke Lee ^{1,17,18,19,20}, Olivier Pourquié ^4,5,6, Woo-Jin Kim ^10,11, Indranil Sinha ³, Su Ryon Shin ^1,21

¹Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA

²Medicinal Materials Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea

³Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

⁴Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA

⁵Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

⁶Harvard Stem Cell Institute, Harvard University, Boston, MA 02138, USA

⁷Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

⁸Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA

⁹Department of Mechanical and Materials Engineering, University of Nebraska, Lincoln, Lincoln, NE 68588, USA

¹⁰Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul 08826, Republic of Korea

¹¹Epigenetic Regulation of Aged Skeleto-Muscular System Laboratory, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 08826, Republic of Korea

¹²Department of Healthcare and Medical Engineering, Chonnam National University, Yeosu 59626, Republic of Korea

¹³Chemical Engineering and Materials Science Department, University of Minnesota, Minneapolis, MN 55455, USA

¹⁴Department of Biological Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates

¹⁵Biotechnology Center (BTC), Khalifa University, Abu Dhabi 127788, United Arab Emirates

¹⁶Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea

¹⁷Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA

¹⁸Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA

¹⁹Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Republic of Korea

²⁰Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Republic of Korea

²¹Lead contact.

²²These authors contributed equally to this work.

Correspondence: Woo-Jin Kim, Indranil Sinha, Su Ryon Shin

Abstract

Engineering biomimetic tissue implants with human induced pluripotent stem cells (hiPSCs) holds promise for repairing volumetric tissue loss. However, these implants face challenges in regenerative capability, survival, and geometric scalability at large-scale injury sites. Here, we present scalable vessel-integrated muscle-like lattices (VMLs), containing dense and aligned hiPSC-derived myofibers alongside passively perfusable vessel-like microchannels inside an endomysium-like supporting matrix using an embedded multimaterial bioprinting technology. The contractile and millimeter-long myofibers are created in mechanically tailored and nanofibrous extracellular matrix-based hydrogels. Incorporating vessel-like lattice enhances myofiber maturation in vitro and guides host vessel invasion in vivo, improving implant integration. Consequently, we demonstrate successful de novo muscle formation and muscle function restoration through a combinatorial effect between improved graft-host integration and its increased release of paracrine factors within volumetric muscle loss injury models. The proposed modular bioprinting technology enables scaling up to centimeter-sized prevascularized hiPSC-derived muscle tissues with custom geometries for next-generation muscle regenerative therapies.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-24)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오소재

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