# Combined Regenerative and Rehabilitation Therapies for Extremity Trauma

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Description: Extremity trauma has been the predominant cause of combat casualties for U.S. armed forces
members in recent military conflicts. These injuries often result in long-term functional disabilities, pain, and
neurologic dysfunction. This proposal will utilize preclinical models of extremity trauma and test new tissue
engineered therapies in combination with rehabilitation regimens. The overall objective of the proposed study
is to establish an integrated regenerative medicine and rehabilitation therapy treatment protocol to enhance
restoration of limb function following severe extremity trauma. The hypothesis is that treatment of large volume
multi-tissue injuries with regenerative engineering strategies that improve revascularization in combination with
low intensity rehabilitation regimens will enhance tissue regeneration, integration, and long term functional
outcomes.
Research Plan: We propose the following Aims: Aim 1: Engineer regenerative muscle constructs using muscle
stem (satellite) cells and microvascular fragments for Volumetric Muscle Loss (VML) injuries; Aim 2: In a VML
model alone, determine if treadmill running rehabilitation enhances the regeneration of large muscle loss treated
with muscle stem cell constructs; Aim 3: In a multi-tissue extremity trauma model, assess the efficacy of
combined treadmill running rehabilitation and regenerative therapies on muscle and bone healing
Methods: We will use preclinical models of extremity trauma, including VML and multi-tissue bone and muscle
defects. In Aim 1 VML injuries will be treated with regenerative muscle therapies including muscle stem cells or
microvascular fragments which will be delivered in collagen hydrogels or decellularized muscle matrices. In Aim
2, treadmill based exercise will be used to test the role of key rehabilitation parameters including timing of
initiation and intensity on graft integration and function. In Aim 3, rehabilitation and regenerative therapies (as
determined in Aim 2 for re-vascularization potency or muscle regeneration potency) will be tested in a multi-
tissue injury model of composite bone and muscle trauma. Outcome measures will include assessments of
muscle and limb structure and function (Aim 1-3) and bone structure and function (Aim 3).
We anticipate the proposed work will result in new insights on rehabilitation protocols for severely injured limbs
and will be communicated through publications and our clinical consultants to impact military and veterans care.

## Key facts

- **NIH application ID:** 10259685
- **Project number:** 5I01RX001985-04
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Nick J Willett
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259685

## Citation

> US National Institutes of Health, RePORTER application 10259685, Combined Regenerative and Rehabilitation Therapies for Extremity Trauma (5I01RX001985-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10259685. Licensed CC0.

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