# Preclinical evaluation of physical and biological interventions to reduce post- traumatic joint contracture

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $468,769

## Abstract

PROJECT SUMMARY
Post-traumatic joint contracture (PTJC) causes debilitating loss of motion following joint injury and is particularly
impactful in the elbow. Clinical treatment is limited due to a poor understanding of key mechanisms leading to
motion loss, making treatment targets elusive. This study will use a validated preclinical animal model of PTJC
to identify the key aspects of physical- and biological-based interventional strategies that best limit PTJC
following injury. Early joint remobilization improves range-of-motion (ROM); however, clinical practice requires a
period of joint immobilization following injury to reduce instability and prevent joint overloading. The parameters
of active therapy (i.e., initiation, duration, intensity) that best limit PTJC after an initial immobilization period
without destabilizing or overloading the healing joint remain unknown. In addition, while studies have shown that
modulation of the inflammatory response can improve healing after joint injury, and that T-cell-mediated signaling
might represent a particularly effective target, protocols guiding inflammation-based therapeutic approaches for
PTJC remain poorly defined. Overall objective: identify fundamental aspects of physical and biological treatment
strategies (i.e., initiation, duration, intensity, synergy) that prevent the development of PTJC using a preclinical
animal model and multi-modal, machine learning (ML)-based analyses. Aim 1: Identify parameters of
voluntary active physical therapy that are most critical to minimizing PTJC while promoting healing after
joint injury. This study will determine the optimal implementation of active physical therapy protocols to best
preserve ROM yet limit load-induced damage. Image-based ML algorithms will be used to automate/accelerate
spatial analysis of joint tissues and advance clustering analyses to elucidate cell- and tissue-level responses to
physical treatments. Hypothesis: moderate intensity/duration physical therapy will maximize motion and limit
joint damage, with additional benefit achieved by implementing a slightly staged increase in intensity after joint
remobilization. Aim 2: Develop biological strategies to reduce PTJC using anti-inflammatory intervention
and targeted modulation of the T cell mediated immune response following joint injury. Anti-inflammatory
prevention strategies will be developed and strategically combined with physical therapy to target multiple
phases of immune-mediated biological activity. ML algorithms will combine multi-modal experimental data to
explore spatial relationships in PTJC pathophysiology. Hypotheses: (i) reducing inflammation in the post-injury
and post-remobilization periods will help preserve ROM; (ii) improved outcomes from blocking T cell activity will
demonstrate a key mechanism of PTJC etiology; (iii) ML-driven data analysis will determine that abrogation of
capsule fibrosis, reduced remobilization-induced ligament hypertrophy, and limited T cell a...

## Key facts

- **NIH application ID:** 10979895
- **Project number:** 1R01AR083378-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Spencer Park Lake
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $468,769
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979895

## Citation

> US National Institutes of Health, RePORTER application 10979895, Preclinical evaluation of physical and biological interventions to reduce post- traumatic joint contracture (1R01AR083378-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979895. Licensed CC0.

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