# Preventing Recurrent Capsular Contracture in Traumatic Elbow Injuries

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $164,631

## Abstract

PROJECT SUMMARY/ABSTRACT
Post-traumatic elbow contracture is a debilitating complication characterized by joint immobility and caused by
thickening and stiffening of the joint capsule. Surgical capsular release is performed when contractures do not
respond to nonsurgical intervention. Capsular release, however, generally only improves (but not normalize)
elbow range of motion. Furthermore, additional fibrosis and contraction often recurs, all of which necessitates
the need to develop better treatment strategies. Joint capsules from post-traumatic elbow contractures have
been found to contain activated myofibroblasts expressing alpha smooth muscle actin (α-SMA) and increased
collagen deposition. In other wound healing scenarios, myofibroblasts exert contractile forces on the ECM and
synthesize collagen in a manner that is modulated in part by mechanical forces and biochemical factors present
in and around the wound. These components interact with the myofibroblasts in a reciprocal and dynamic
manner, such that wound healing proceeds as a mechano-chemical feedback loop that resolves with either
normal or pathological healing. We hypothesize that this feedback loop is also operational in the injured joint
capsule and contributes to capsule thickening and contracture. Our strategy is to interrupt this feedback loop by
temporarily blocking NMMII-actin engagement, and thus the ability of myofibroblasts to generate and sense force
at critical points during wound healing by delivering the drug blebbistatin (or its derivatives) to the wound site via
poly(lactide-co-gylcolide) (PLGA) particles. This project has two major aims that are centered on developing a
mechanistic understanding of the feedback loop in the joint capsule and assessing the feasibility of using small
molecules to interrupt this feedback loop and reduce/eliminate fibrosis and contracture. In aim 1, we will perform
a series of in vitro experiments where we compare blebbistatin and para-nitroblebbistatin PLGA particle
compositions and release kinetics to remodeling outcomes, such as myofibroblast activation, force generation,
myofibroblast activation, collagen production, and ECM remodeling/tissue stiffness. In aim 2, we will test the
ability of blebbistatin or para-nitroblebbistatin to mitigate joint capsule thickening/stiffening, contracture, and
fibrosis in a validated rat model of elbow joint contracture. We envision that inhibition of NMMII activity with
blebbistatin/para-blebbistatin can be used adjunctively to capsule release surgery. We hypothesize that the
controlled-release of drug will temper myofibroblast behavior so that more normal healing follows and larger
gains in post-operative ROM are maintained. The knowledge gained here will also have implications for other
joints (e.g., knee, ankle, finger) and fibrotic conditions.

## Key facts

- **NIH application ID:** 9891331
- **Project number:** 1R21AR075137-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** EDWARD A SANDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $164,631
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891331

## Citation

> US National Institutes of Health, RePORTER application 9891331, Preventing Recurrent Capsular Contracture in Traumatic Elbow Injuries (1R21AR075137-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9891331. Licensed CC0.

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