# Sex-based Muscular Adaptations, Capillary dysfunction and functional decline impact Knee-related psychosocial outcomes after acute knee injury (SMACK)

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $627,318

## Abstract

Abstract
Following an Anterior Cruciate Ligament (ACL) reconstruction, females have worse outcomes; however,
skeletal muscle biology and function have preferentially been studied in males. These observations suggest
that there are sex-based differences in the biological mechanisms contributing to recovery of muscle function.
Intriguing pilot data in this proposal show preferential impairment in the recovery of quadriceps muscle and
function and diminished psychosocial recovery in females as compared to males following ACL reconstruction.
This proposal seeks to test the novel hypothesis that following an ACL injury, females experience exaggerated
muscle cellular and molecular deficits, hindering their recovery of strength, resulting in pronounced deficiencies
in gait mechanics and disproportionally worse psychosocial recovery compared to males. By identifying the
cellular and molecular foundation of sex-based differences, subsequent clinical trials can test sex specific
approaches to improve outcomes for women after ACL injury. We will in Aim 1 define the molecular, cellular
and morphological sex-based differences in quadriceps muscle after ACL injury and reconstruction. In Aim 2
determine the effect of sex on knee function after an ACL reconstruction. Lastly, in Aim 3 will determine the
timing and magnitude of psychosocial recovery differences between females and males following an ACL
reconstruction. Results from this work will exert an immediate impact on clinical practice guidelines, as well as
identify critical therapeutic targets needed to propel subsequent evidence-based clinical trials designed to
improve rehabilitative outcomes for females.

## Key facts

- **NIH application ID:** 10667310
- **Project number:** 5R01AR078316-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Christopher Fry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,318
- **Award type:** 5
- **Project period:** 2021-08-05 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667310

## Citation

> US National Institutes of Health, RePORTER application 10667310, Sex-based Muscular Adaptations, Capillary dysfunction and functional decline impact Knee-related psychosocial outcomes after acute knee injury (SMACK) (5R01AR078316-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10667310. Licensed CC0.

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