# Engineering Highly Functional Pre-Vascularized Human Skeletal Muscle for In Vitro and In Vivo Applications

> **NIH NIH F31** · DUKE UNIVERSITY · 2022 · $39,508

## Abstract

Abstract
 Current models of engineered human skeletal muscle mainly consist of myogenic cells and fibroblasts
which are grown in various types of natural or synthetic biomaterial scaffolds. The simplified cellular makeup of
these tissues can limit their utility in disease modeling and regenerative therapies, which can be improved by
incorporating additional muscle-resident cell types such as vascular cells. However, to date, no studies have
demonstrated successful in vitro vascularization of mature functional engineered muscle without loss of
contractile function. The Bursac lab has been the first to engineer contractile human skeletal muscle tissues
(“myobundles”) made of primary human myoblasts or induced pluripotent stem cell-derived muscle progenitors.
My preliminary results show that under optimized conditions, mixing myoblasts with 5% endothelial progenitor
cells (EPCs) at the time of tissue formation produces vascularized tissues with contractile function comparable
to that of muscle-only controls. Importantly, with time of culture, robust vascular networks formed throughout the
myobundle volume undergo early lumen formation. Building on these promising results, I will test the hypotheses
that engineering dense capillary networks inside highly functional engineered human muscle will: 1) support the
maintenance of the muscle stem cell (satellite cell, SC) niche and enhance in vitro regenerative capacity of
myobundles and 2) accelerate vascularization and perfusion of myobundle implants to improve their survival and
therapeutic efficacy in volumetric muscle loss (VML) injury model in vivo. Specifically, I will characterize the effect
of myobundle-EPC coculture on the transcriptomic profile of resident SCs using single cell RNA-sequencing and
will investigate vascularization-induced changes in SC activation and muscle regeneration in response to a toxin
injury. In immunocompromised mice in vivo, I will analyze how establishment of blood flow through pre-
vascularized myobundle implants affects SC phenotype and will further assess potential of implanted
myobundles to induce repair of VML injury in the tibialis anterior muscle. If successful, this work will establish
the first biomimetic model of highly functional, vascularized human skeletal muscle tissue and will provide a
foundation for future pursuits of engineered muscle therapies for VML.

## Key facts

- **NIH application ID:** 10535766
- **Project number:** 1F31AR080574-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Torie M Broer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,508
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535766

## Citation

> US National Institutes of Health, RePORTER application 10535766, Engineering Highly Functional Pre-Vascularized Human Skeletal Muscle for In Vitro and In Vivo Applications (1F31AR080574-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10535766. Licensed CC0.

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