Actuated tissue engineered muscle grafts restore functional mobility after volumetric muscle loss
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Author(s)
Rousseau, Erin
Raman, Ritu
Tamir, Tigist
Bu, Angel
Srinivasan, Shriya
Lynch, Naomi
Langer, Robert
White, Forest M.
Cima, Michael J.
Date Issued
November 2023
Journal
Biomaterials
Publisher
Elsevier BV
Citation
Rousseau, Erin, Raman, Ritu, Tamir, Tigist, Bu, Angel, Srinivasan, Shriya et al. 2023. "Actuated tissue engineered muscle grafts restore functional mobility after volumetric muscle loss." Biomaterials, 302.
Version
Final published version
Abstract
Damage that affects large volumes of skeletal muscle tissue can severely impact health, mobility, and quality-of-life. Efforts to restore muscle function by implanting tissue engineered muscle grafts at the site of damage have demonstrated limited restoration of force production. Various forms of mechanical and biochemical stimulation have been shown to have a potentially beneficial impact on graft maturation, vascularization, and innervation. However, these approaches yield unpredictable and incomplete recovery of functional mobility. Here we show that targeted actuation of implanted grafts, via non-invasive transcutaneous light stimulation of optogenetic engineered muscle, restores motor function to levels similar to healthy mice 2 weeks post-injury. Furthermore, we conduct phosphoproteomic analysis of actuated engineered muscle in vivo and in vitro to show that repeated muscle contraction alters signaling pathways that play key roles in skeletal muscle contractility, adaptation to injury, neurite growth, neuromuscular synapse formation, angiogenesis, and cytoskeletal remodeling. Our study uncovers changes in phosphorylation of several proteins previously unreported in the context of muscle contraction, revealing promising mechanisms for leveraging actuated muscle grafts to restore mobility after volumetric muscle loss.
Subjects
Mechanics of Materials
Biomaterials
Biophysics
Ceramics and Composites
Bioengineering
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2023.122317
