Engineering large-scale hiPSC-derived vessel-integrated muscle-like lattices for enhanced volumetric muscle regeneration

Myung Chul Lee, Yasamin A. Jodat, Yori Endo, Alejandra Rodríguez-delaRosa, Ting Zhang, Mehran Karvar, Ziad Al Tanoury, Jacob Quint, Tom Kamperman, Kiavash Kiaee, Sofia Lara Ochoa, Kun Shi, Yike Huang, Montserrat Pineda Rosales, Adnan Arnaout, Hyeseon Lee, Jiseong Kim, Eder Luna Ceron, Isaac Garcia Reyes, Adriana C. PanayiAngel Flores Huidobro Martinez, Xichi Wang, Ki Tae Kim, Jae I. Moon, Seung Gwa Park, Kangju Lee, Michelle A. Calabrese, Shabir Hassan, Junmin Lee, Ali Tamayol, Luke Lee, Olivier Pourquié, Woo Jin Kim, Indranil Sinha, Su Ryon Shin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1715-1744
Number of pages30
JournalTrends in Biotechnology
Volume42
Issue number12
DOIs
StatePublished - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Ltd

Keywords

  • bioprinting
  • engineering vascularized tissues
  • induced pluripotent stem cells
  • secreted factors, volumetric muscle loss
  • skeletal muscle engineering

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