# Regenerative Rehabilitative Principles in Modulating Weight Bearing and Joint Kinematics to Delay Post-Traumatic Knee Osteoarthritis

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2024 · $383,980

## Abstract

PROJECT S
U
MMARY
 Knee injuries, e.g., meniscus tears, increase the risk of developing post-traumatic osteoarthritis (PTOA)
by at least 10 fold. PTOA leads to disability with a substantial healthcare cost of $3 billion per year in the US.
Although rehabilitation is required after injury, current protocols only address the return to pre-injury activities.
Critical knowledge gaps exist regarding how to optimize early rehabilitation efforts to preserve long-term
knee cartilage health. Using a well-established rat PTOA model, we propose to characterize responses of knee
cartilage to the manipulation of three elements commonly implemented during post-injury rehabilitation: 1)
durations of initial non-weight bearing, 2) modifications of physical activity level, and 3) deviations in lower-limb
joint kinematics. The use of a pre-clinical rat model provides the experimental control over disease timeline to
facilitate a mechanistic study to understand PTOA. Our overall hypothesis is that post-injury interventions
that emphasize maintaining pre-injury knee loading profile (e.g. minimizing weight-bearing restriction,
regaining physical activity level, or reducing deviations in joint kinematics) will delay PTOA. We will
systematically test this hypothesis using innovative experimental approaches and technologies to address the
knowledge gaps in the PTOA rehabilitation literature as described in the following Aims. (Aim 1) Non-weight
bearing durations in rats after the medial meniscal transection (MMT) surgery performed on the left hind limb
will be varied using hind-limb suspension. The comparisons of cartilage health among varying exposures of
suspension determines the causal effect of initial non-weight bearing on PTOA progression. The use of hind-
limb suspension instead of limb immobilization reduces harmful consequences of joint contracture and is more
in line with current practice of prescribing initial non-weight bearing after knee injuries. (Aim 2) Post-injury
physical activity levels will be modified by varying the amount of daily treadmill running. Rats’ pre-injury
activity levels will first be established to allow standardized quantification of post-injury activity modification (%
of pre-MMT). The causal effect of post-injury activity level on PTOA progression can then be determined. (Aim
3) 3D hind-limb joint kinematics will be assessed using biplanar X-ray motion analysis at multiple time points
before and after MMT to determine whether early post-injury joint kinematic deviations are predictive of the
ultimate severity of PTOA. Using X-ray videos to directly quantify 3D bone movements can overcome the
significant errors associated with the use of skin markers. For all three Aims, we will incorporate our contrast
enhanced microCT analysis with conventional histopathology to provide complementary evaluations of the 3D
microstructure/compositions of knee cartilage. Findings from this innovative work will provide insight into the
potential causal e...

## Key facts

- **NIH application ID:** 10778604
- **Project number:** 5R01AR080154-03
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Liang-Ching Tsai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $383,980
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778604

## Citation

> US National Institutes of Health, RePORTER application 10778604, Regenerative Rehabilitative Principles in Modulating Weight Bearing and Joint Kinematics to Delay Post-Traumatic Knee Osteoarthritis (5R01AR080154-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10778604. Licensed CC0.

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