# Muscle-macrophage constructs for skeletal muscle repair

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $384,780

## Abstract

Successful engineering of biomimetic skeletal muscle tissues could allow creation of accurate
models of muscle physiology and disease and aid treatment of various muscle disorders. This project
is based on our recently developed methods to utilize adult rat myogenic cells for engineering of 3D
skeletal muscle tissues with structural and functional properties comparable to those of native muscle.
Specifically, we have established conditions for robust in vitro expansion of adult rat myogenic cells
and have successfully utilized them to engineer skeletal muscle tissues with contractile capacity 10-
100 fold higher than previously reported. Importantly, in a comprehensive set of preliminary studies we
for the first time show that self-regenerative capacity of adult-derived engineered muscle in vitro and
survival in vivo can be significantly enhanced by a 3-D co-culture of skeletal muscle progenitors with
non-polarized macrophages derived from bone marrow. We propose to build on these exciting results
and systematically explore the use of 3D muscle-macrophage co-culture system to create highly
contractile and regenerative muscle tissues with the capacity for rapid vascular and neuronal integration
and successful repair of skeletal muscle injury in vivo. We will study: (1) the cellular and molecular
mechanisms of macrophage mediated self-repair of tissue-engineered muscle in vitro, (2) the combined
effects of macrophages, vascular cells, and biophysical cues on the ability of in vitro formed pre-
vascularized engineered muscle to undergo rapid blood perfusion and functional maturation in vivo,
and (3) the roles of macrophage supplementation and synaptogenic stimulation in vitro upon the ability
of muscle-macrophage implants to functionally integrate with and repair damaged skeletal muscle in
vivo. Successful completion of the proposed studies will establish foundation for the future applications
of tissue engineering methodologies to human muscle repair. Furthermore, our novel strategy to utilize
immune system cells as pro-regenerative adjuvants inside tissue-engineered implants may find broad
applications in the field of regenerative medicine.

## Key facts

- **NIH application ID:** 9985734
- **Project number:** 5R01AR070543-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nenad Bursac
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,780
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985734

## Citation

> US National Institutes of Health, RePORTER application 9985734, Muscle-macrophage constructs for skeletal muscle repair (5R01AR070543-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985734. Licensed CC0.

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