# The role of mechanical stimulation in macrophage-mediated skeletal muscle regeneration in an in vitro injury model

> **NIH NIH F31** · HARVARD UNIVERSITY · 2021 · $32,947

## Abstract

Project Summary/Abstract
Severe muscle injuries resulting from trauma, strain, or contusion are very common yet still present a significant
clinical challenge since there is no therapy currently available to restore full function to the damaged tissue.
Instead, severe muscle injuries often heal via fibrosis, leading to contracture, pain, and disability. Since skeletal
muscle is known to respond strongly to mechanical stimuli, recent studies have shown that the use of mechanical
cues alone can effectively stimulate tissue regeneration. Investigation has provided evidence that the immune
system, which plays a critical role in tissue repair, may be modulated by mechanical stimulation of the injured
tissue. In this proposal, I will focus on investigating the role of mechanical signaling in immune cell-muscle
interactions, specifically between macrophages and muscle progenitor cells (MPCs) since macrophages have
been shown to play an important role in guiding MPC behavior during repair. I hypothesize that the regenerative
effects of macrophages on injured skeletal muscle through their interactions with MPCs will be enhanced under
specific conditions of applied cyclic tensile loading leading to improved recovery. I will develop an in vitro model
of injured skeletal muscle containing myofibers and MPCs and introduce polarized macrophages into this
system. I will design and fabricate a cyclic tensile loading device and use this system to explore the effects of
cyclic tensile loading parameters, such as strain and frequency, on macrophage modulation of myofiber
regeneration and functional repair of the injured skeletal muscle constructs. I will further evaluate potential
mechanisms behind the observed results to understand how mechanical cues may be impacting the interaction
between macrophages and MPCs. I hope that the proposed work can offer new insight into how mechanical
stimulation can be used clinically as a method of promoting skeletal muscle repair. The knowledge that arises
from these studies may enable the optimization of physical therapies to provide better outcomes in the clinical
setting and may offer new therapeutic avenues for healing severe muscle injuries.

## Key facts

- **NIH application ID:** 10196946
- **Project number:** 5F31AR075367-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Stephanie McNamara
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,947
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196946

## Citation

> US National Institutes of Health, RePORTER application 10196946, The role of mechanical stimulation in macrophage-mediated skeletal muscle regeneration in an in vitro injury model (5F31AR075367-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196946. Licensed CC0.

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