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

a Relationship between maximum isometric tetanic force measured ex vivo and muscle mass in mouse TAs. Control muscles are designated as “VML？ Scaffold？ Cells？”. In the VML injury groups, muscles were partially excised and left untreated (VML+ Scaffold？ Cells？) or implanted with either a tissue-engineered bioconstruct comprising of scaffold alone (VML+ Scaffold+ Cells？) or with scaffold and muscle stem cells, and muscle-resident cells (VML+ Scaffold+ Cells+). “VML+ Scaffold+ Cells+” muscles showed proportionally increased mass and, statistically significant, force (Table (Table1),1), consistent with functional active stress generation in the newly formed tissue. b Active twitch force across a range of muscle lengths. (Left panel) In vivo measurements. (Right panel) Ex vivo measurements. The “VML+ Scaffold？ Cells？” muscles have narrowed length-tension curves (comparisons between VML+ Scaffold+ Cells？ group and VML+ Scaffold+ Cells+ or VML？ Scaffold？ Cells？ groups; p？<？0.0001). The length-tension curves of the “VML+ Scaffold+ Cells+” muscles were restored with treatment, meaning that a greater fraction of the maximum force was generated over a broader range of muscle lengths. No improvement was observed with “VML+ Scaffold+ Cells？” treatment. The curve from each muscle was normalized by its own maximum force and centered at optimal length. Symbols are the mean forces and error bars represent SEM (n？=？6–9 muscles per group