Publication

Nanofiber-Based Delivery of Bioactive Lipids Promotes Pro-regenerative Inflammation and Enhances Muscle Fiber Growth After Volumetric Muscle Loss

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Last modified
  • 05/14/2025
Type of Material
Authors
    Cheryl L. San Emeterio, Georgia Institute of TechnologyLauren A. Hymel, Georgia Institute of TechnologyThomas C. Turner, Georgia Institute of TechnologyMolly E. Ogle, Georgia Institute of TechnologyEmily G. Pendleton, University of GeorgiaWilliam Y. York, Georgia Institute of TechnologyClaire E. Olingy, Georgia Institute of TechnologyAlan Y. Liu, Georgia Institute of TechnologyHong Seo Lim, Georgia Institute of TechnologyTodd A. Sulchek, Georgia Institute of TechnologyGordon L. Warren, Georgia State UniversityLuke J. Mortensen, University of GeorgiaPeng Qiu, Georgia Institute of TechnologyYoung Jang, Emory UniversityNick Willett, Emory UniversityEdward Botchwey, Emory University
Language
  • English
Date
  • 2021-03-19
Publisher
  • Frontiers Media SA
Publication Version
Copyright Statement
  • © 2021 San Emeterio, Hymel, Turner, Ogle, Pendleton, York, Olingy, Liu, Lim, Sulchek, Warren, Mortensen, Qiu, Jang, Willett and Botchwey.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 9
Start Page
  • 650289
End Page
  • 650289
Grant/Funding Information
  • This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant Nos. DGE-1650044 and DGE-1148903 as well as by the NIH under award numbers R01AR071708 and R56DE029703, the NIH Cell and Tissue Engineering Training grant under award number GM008433, and the American Heart Association Grant 15PRE25090024.
Supplemental Material (URL)
Abstract
  • Volumetric muscle loss (VML) injuries after extremity trauma results in an important clinical challenge often associated with impaired healing, significant fibrosis, and long-term pain and functional deficits. While acute muscle injuries typically display a remarkable capacity for regeneration, critically sized VML defects present a dysregulated immune microenvironment which overwhelms innate repair mechanisms leading to chronic inflammation and pro-fibrotic signaling. In this series of studies, we developed an immunomodulatory biomaterial therapy to locally modulate the sphingosine-1-phosphate (S1P) signaling axis and resolve the persistent pro-inflammatory injury niche plaguing a critically sized VML defect. Multiparameter pseudo-temporal 2D projections of single cell cytometry data revealed subtle distinctions in the altered dynamics of specific immune subpopulations infiltrating the defect that were critical to muscle regeneration. We show that S1P receptor modulation via nanofiber delivery of Fingolimod (FTY720) was characterized by increased numbers of pro-regenerative immune subsets and coincided with an enriched pool of muscle stem cells (MuSCs) within the injured tissue. This FTY720-induced priming of the local injury milieu resulted in increased myofiber diameter and alignment across the defect space followed by enhanced revascularization and reinnervation of the injured muscle. These findings indicate that localized modulation of S1P receptor signaling via nanofiber scaffolds, which resemble the native extracellular matrix ablated upon injury, provides great potential as an immunotherapy for bolstering endogenous mechanisms of regeneration following VML injury.
Author Notes
Keywords
Research Categories
  • Health Sciences, Immunology
  • Engineering, Biomedical
  • Health Sciences, Rehabilitation and Therapy

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