hiPSC-derived 3D Bioprinted Skeletal Muscle Tissue Implants Regenerate Skeletal Muscle Following Volumetric Muscle Loss

Yasamin A. Jodat, Ting Zhang, Ziad Al Tanoury, Tom Kamperman, Kun Shi, Yike Huang, Adriana Panayi, Yori Endo, Xichi Wang, Jacob Quint, Adnan Arnaout, Kiavash Kiaee, Shabir Hassan, Junmin Lee, Angel Flores Huidobro Martinez, Sofia Lara Ochoa, KangJu Lee, Michelle Calabrese, Alessandro Carlucci, Ali TamayolIndranil Sinha, Olivier Pourquié, Su Ryon Shin

Research output: Working paper

Abstract

Engineering of biomimetic tissue implants provides an opportunity for repairing volumetric muscle loss (VML), beyond a tissue’s innate repair capacity. Here, we present thick, suturable, and pre-vascularized 3D muscle implants containing human induced pluripotent stem cell-derived myogenic precursor cells (hiPSC-MPCs), which can differentiate into skeletal muscle cells while maintaining a self-renewing pool. The formation of contractile myotubes and millimeter-long fibers from hiPSC-MPCs is achieved in chemically, mechanically, and structurally tailored extracellular matrix-based hydrogels, which can serve as scaffolds to ultimately organize the linear fusion of myoblasts. Embedded multi-material bioprinting is used to deposit complex patterns of perfusable vasculatures and aligned hiPSC-MPC channels within an endomysium-like supporting gel to recapitulate muscle architectural integrity in a facile yet highly rapid manner. Moreover, we demonstrate successful graft-host integration and de novo muscle formation upon in vivo implantation of pre-vascularized constructs within a VML model. This work pioneers the engineering of large pre-vascularized hiPSC-derived muscle tissues toward next generation VML regenerative therapies.
Original languageEnglish
PublisherResearch Square Publications
DOIs
Publication statusAccepted/In press - 20 Jan 2021

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