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NPJ Regen Med. 2018 Oct 10;3:18. doi: 10.1038/s41536-018-0057-0. eCollection 2018.

Biomechanics show stem cell necessity for effective treatment of volumetric muscle loss using bioengineered constructs.

Quarta M#1,2,3,4, Cromie Lear MJ#1,2,3, Blonigan J1,2,3, Paine P1,2,3, Chacon R1,2,3, Rando TA1,2,3.

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1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305 USA.
2Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305 USA.
Center for Tissue Regeneration, Restoration and Repair, Veterans Affairs Hospital, Palo Alto, CA 94036 USA.
4Molecular Medicine Research Institute, Sunnyvale, CA 94085 USA.
Contributed equally


Despite the regenerative capacity of muscle, tissue volume is not restored after volumetric muscle loss (VML), perhaps due to a loss-of-structural extracellular matrix. We recently demonstrated the structural and functional restoration of muscle tissue in a mouse model of VML using an engineered "bioconstruct," comprising an extracellular matrix scaffold (decellularized muscle), muscle stem cells (MuSCs), and muscle-resident cells (MRCs). To test the ability of the cell-based bioconstruct to restore whole-muscle biomechanics, we measured biomechanical parameters in uninjured muscles, muscles injured to produce VML lesions, and in muscles that were injured and then treated by implanting either the scaffolds alone or with bioconstructs containing the scaffolds, MuSCs, and MRCs. We measured the active and passive forces over a range of lengths, viscoelastic force relaxation, optimal length, and twitch dynamics. Injured muscles showed a narrowed length-tension curve or lower force over a narrower range of muscle lengths, and increased passive force. When treated with bioconstructs, but not with scaffolds alone, injured muscles showed active and passive length-tension relationships that were not different from uninjured muscles. Moreover, injured muscles treated with bioconstructs exhibited reduced fibrosis compared to injured muscles either untreated or treated with scaffolds alone. The cell-based bioconstruct is a promising treatment approach for future translational efforts to restore whole-muscle biomechanics in muscles with VML lesions.

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