Biofabricating murine and human myo-substitutes for rapid volumetric muscle loss restoration

Marco Costantini, Stefano Testa, Ersilia Fornetti, Claudia Fuoco, Carles Sanchez Riera, Minghao Nie, Sergio Bernardini, Alberto Rainer, Jacopo Baldi, Carmine Zoccali, Roberto Biagini, Luisa Castagnoli, Libero Vitiello, Bert Blaauw, Dror Seliktar, Wojciech Święszkowski, Piotr Garstecki, Shoji Takeuchi, Gianni Cesareni, Stefano CannataCesare Gargioli

Research output: Contribution to journalArticlepeer-review

Abstract

The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions—pivotal aspects for cell survival and muscle contractile functionalities—together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

Original languageEnglish
Article numbere12778
JournalEMBO Molecular Medicine
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 5 2021

Keywords

  • bioprinting
  • skeletal muscle
  • stem cells
  • tissue engineering
  • VML

ASJC Scopus subject areas

  • Molecular Medicine

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