# Biomaterial Implants for the Treatment of Disuse Muscle Atrophy

> **NIH VA I21** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Disabilities secondary to long term immobilization are a major cause of morbidity and escalating
healthcare costs for the VA. Immobilization is a complication of many conditions (e.g. limb injury, bed
rest) and results in mechanical unloading of skeletal muscles. In response to mechanical unloading,
muscles undergo a rapid loss of mass, referred to as disuse atrophy. Disuse atrophy prolongs the
rehabilitation period, increasing the risk that full functional recovery will not be achieved. The current
rehabilitation course for disuse atrophy encompasses resistance exercise paradigms designed to
promote muscle growth, but many VA patients with atrophy are advanced aged and too frail to
successfully complete the training. The inability to rehabilitate will spur a vicious cycle of decreased
activity and loss of mobility, impacting quality of life. Thus, rehabilitating atrophied muscle remains a
highly relevant therapeutic target. Systemic delivery of insulin-like growth factor 1 (IGF-1), as well as
other factors (e.g. leptin and adiponectin), increases muscle mass; however, systemic delivery is
hindered by cost, off target effects, and patient compliance with the dosing schedule. Recently,
bioengineers are addressing these issues with drug delivery systems that enable localized, sustained
release of a therapeutic. While these devices may prove successful to some extent, maximal
functional recovery is likely to require a more complex combination of factors delivered at
physiological concentrations over physiological timescales, which is difficult to achieve with current
technologies. To address these limitations, this work will develop devices to engineer the adipose
tissue, a readily available tissue source, to release factors in the most ideal proportions that promote
growth of atrophied muscle. Indeed, adipose tissues secrete biomolecules that act at the systemic
level. In order to modulate the adipose secretome, we have developed tissue engineering scaffolds
for implant into the adipose tissue using the biodegradable polymer poly(lactide-co-glycolide). This
material is used in FDA approved devices including sutures and bone screws. Scaffold implant into
visceral fat of mice elevates IGF-1 expression. Concurrently, gene expression involved in muscle
growth is activated in the gastrocnemius. This data motivates the hypothesis that specifically
designed scaffolds can promote a muscle-supportive secretome when implanted into fat and this
approach will enhance functional recovery in mice with disuse atrophy. Aim 1 of the proposed work
will improve our understanding of how the scaffold functions by investigating if alterations in the
adipose secretome is biomaterial specific. This aim will also advance the scaffold’s translational
relevance by determining if a muscle regenerative secretome exists when the implant site is
subcutaneous fat. Aim 2 will determine if scaffold implant in aged mice with atrophied muscle from
hindlimb immobilization enhances fun...

## Key facts

- **NIH application ID:** 9890541
- **Project number:** 1I21RX003191-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Robert Michael Gower
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890541

## Citation

> US National Institutes of Health, RePORTER application 9890541, Biomaterial Implants for the Treatment of Disuse Muscle Atrophy (1I21RX003191-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890541. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*