# Physical and Biological Treatment Strategies to Prevent Post-Traumatic Joint Contracture

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $335,500

## Abstract

PROJECT SUMMARY
Post-traumatic joint contracture (PTJC) often leads to debilitating impairment following injury, especially in the
elbow where even minor injuries can lead to drastic disability. PTJC is a challenging clinical condition that is
difficult to reverse, so preventative treatment strategies are urgently needed. Mechanisms governing
successful physical therapy are poorly understood; systematic evaluation is needed to determine the potential
of physical rehabilitation. Several drugs have demonstrated anti-fibrotic effects in other systems; focused
studies are needed to evaluate if biological therapy using these drugs is able to reduce PTJC. Also, the
potential synergistic impact of combined physical/biological therapies is unknown. The objective of this study is
to utilize a validated animal model of PTJC to investigate physical and biological strategies to preserve
mechanics/function (e.g., range of motion and gait patterns) of the elbow joint following injury. SA1: Determine
if physical treatments can prevent PTJC and preserve mechanics/function of injured elbows. We will
identify whether active motion is successful in reducing PTJC, and determine which governing principles best
preserve joint mechanics. Hypothesis: Low-intensity, long-duration physical therapy will be most effective at
preserving joint mechanics and function by reducing excessive ECM deposition and tissue fibrosis, while also
limiting potential joint wear from high-intensity therapy. SA2: Determine if biological treatments can prevent
PTJC and preserve mechanics/function of injured elbows. We will investigate whether the pleiotropic anti-
fibrotic effects of simvastatin and losartan can prevent PTJC and identify which treatment protocol best
preserves joint mechanics/function. Hypothesis: Both simvastatin and losartan will reduce PTJC severity but a
combination of low doses of both drugs will be most effective in preserving joint mechanics and function by
reducing the fibrotic response in joint tissues, especially by limiting post-traumatic collagen production. SA3:
Determine if synergistic and/or compensatory effects of a combined physical-biological treatment
strategy can maintain elbow joint mechanics/function at pre-injury levels. We will investigate the degree
to which a well-designed physical therapy protocol (from Aim 1) combined with strategic biological intervention
(from Aim 2) can eliminate symptoms of PTJC. Hypothesis: Treatment aimed at both limiting the fibrotic
biological response via drug therapy and disrupting fibrosis via physical therapy will be most effective in
preserving joint mechanics/function by limiting tissue fibrosis due to synergistic and compensatory benefits of
combined therapy. Successful completion of this study will elucidate treatment principles that best prevent
contracture and dysfunction after injury via clinically-available physical, biological, and/or combined treatment
strategies. Results will be impactful for understanding eti...

## Key facts

- **NIH application ID:** 9750078
- **Project number:** 5R01AR071444-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Spencer Park Lake
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,500
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9750078

## Citation

> US National Institutes of Health, RePORTER application 9750078, Physical and Biological Treatment Strategies to Prevent Post-Traumatic Joint Contracture (5R01AR071444-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9750078. Licensed CC0.

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