# Regenerative engineering for complex extremity trauma

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $41,658

## Abstract

PROJECT SUMMARY
 The clinical treatment of limb threatening injuries requires complex surgical management and a lifetime
of corrective surgeries and physical therapy. There is an unmet clinical need for regenerative approaches that
can functionally repair both muscle and adjacent bone. Our prior research has shown that spatial patterning cues
from nanoscale extracellular matrices modulate the cellular inflammatory phenotype, angiogenic potential, and
skeletal muscle myogenesis. We have further shown that when these patterned materials are combined with
running exercise, that large volumetric muscle injuries in mice can be regenerated comparable to native tissue.
Therefore, the goal of the parent grant, was to define the regenerative relationship between bone and muscle
healing as well as couple engineered muscle with free running exercise to enhance local tissue regeneration.
The overarching research goal of this supplement is to identify the characteristics of an optimal exercise regime
for rehabilitation and regeneration after complex traumatic injury and co-treatment with an engineered muscle.
This will be explored through the application of a comprehensive post-injury exercise regimen that varies in
duration, frequency, intervention type, and timing. The proposal first examines the contribution of exercise
frequency (sessions per week) and duration (length of each session) on tissue regeneration and limb functional
recovery. This approach will allow us to determine the impact of fatigue and recovery time on a diverse set of
healing outcomes which include in situ muscle force production, microCT imaging to evaluate bone density and
volume, dynamic weight bearing and tactile allodynia to assess mobility and pain, and systemic inflammatory
cytokine profiling. We will also examine how different forms of exercise intervention (contraction and loading)
and timing (how soon after injury) guide these same regenerative outcomes. The research outcomes of the
proposed body of work for this supplement will: 1) generate new data on rehabilitation protocols that extends
beyond free running; 2) expands the capacity of healing metrics to examine dynamic weight bearing and pain
sensitization as primary functional health assessments; 3) characterizes the immune profile of circulating
cytokines in response to injury and exercise. The proposed studies will establish an effective rehabilitation
protocol that works in concert with our engineered muscle therapy to enhance the regenerative response to
rehabilitation therapies following severe musculoskeletal injury. This award supplement will provide training in
research and career development to support the mission of promoting diversity in health-related research. The
proposed candidate, Joshua Vanderpool, will receive training in muscle biology, biomaterial fabrication, cell
culture, exercise physiology, animal injury and behavioral models, in vivo imaging, histology, and image analysis.
Additionally, they will r...

## Key facts

- **NIH application ID:** 11074358
- **Project number:** 3R01AR080150-02S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Karina Nakayama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,658
- **Award type:** 3
- **Project period:** 2024-05-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11074358

## Citation

> US National Institutes of Health, RePORTER application 11074358, Regenerative engineering for complex extremity trauma (3R01AR080150-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11074358. Licensed CC0.

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