# Competition between Resistance Training and Inflammation in an On-Chip Skeletal Muscle Microtissue Model of Sepsis

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2023 · $234,816

## Abstract

PROJECT SUMMARY
Chronic and acute inflammation are significant contributors to skeletal muscle pathology in multiple diseases.
Severe inflammation associated with sepsis has profound short- and long-term effects on muscle. Sepsis is
characterized by a dysregulated immune response to infection that can alter muscle force generation, wasting,
and bioenergetics. Survivors of sepsis have increased risk for the development of persistent acquired weakness
syndromes. The inflammatory response in sepsis is mediated by the release of pro-inflammatory cytokines,
including tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β). While we know that sepsis-induced
changes in skeletal muscle are associated with inflammation, the mechanisms underlying muscle dysfunction in
sepsis are not well understood, and there is a significant need to capture the evolution of these impairments to
establish effective treatment strategies. Harnessing in vitro models of cytokine-induced myopathy in human
skeletal muscle can inform and elucidate fundamental mechanisms of pathology in sepsis enabling development
of effective treatments. Resistance training is a widely accepted prescriptive treatment for rebuilding muscle
strength and mass. However, post-recovery resistance training has minimal long-term effects in many sepsis
patients, and recent studies suggest that early (pre-recovery) physical therapy may preserve muscle fiber cross-
sectional area though not strength, indicating a need for further analysis of the complex evolution of sepsis. This
evidence formed the cornerstone of our hypothesis that inflammation limits the therapeutic effects of resistance
training, which will be tested in a 3D in vitro organoid model through the following specific aims: 1) Establish an
in vitro model of sepsis using human SMMT to capture temporal impairments in response to pro-inflammatory
agents; 2) Determine recovery of contractile function and structure of engineered SMMT in response to
resistance training following exposure to pro-inflammatory agents. The proposed technical innovation and study
is important because it will inform the fundamental basis of sepsis-induced myopathies and the potential role of
resistance training to ameliorate post-sepsis effects. These results will positively impact future treatment of
sepsis and improve the quality of life of post-sepsis survivors.

## Key facts

- **NIH application ID:** 10569534
- **Project number:** 5P20GM139760-03
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Elise Anne Corbin
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $234,816
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569534

## Citation

> US National Institutes of Health, RePORTER application 10569534, Competition between Resistance Training and Inflammation in an On-Chip Skeletal Muscle Microtissue Model of Sepsis (5P20GM139760-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10569534. Licensed CC0.

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