# Natural Variation in the Growth and Development of the ACL Complex

> **NIH NIH R00** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $241,512

## Abstract

Identifying risk factors to prevent anterior cruciate ligament (ACL) injuries remains a major objective of
musculoskeletal research. Athletic participation in the United States among children and adolescents has
increased over the last three decades, resulting in a greater prevalence of ACL injuries. The frequency of ACL
injuries among individuals under 15 years of age has risen 924% since 1994 despite the incorporation of injury
prevention programs in youth sports. Further, 70% of ACL injuries occur while performing non-contact
maneuvers (e.g. single foot landings, pivots). Yet, it remains unclear whether these injuries result from a single
overload event or a fatigue failure wherein a period of intervention is available. Injuries are likely multifactorial
and influenced by an individual’s natural anatomical variation. Fatigue failure of the ACL via repetitive loading,
combined with the natural variation in anatomical structure between individuals, has largely been overlooked
as an explanatory mechanism for unanticipated ACL failures. We showed previously that ACL cross-sectional
area (CSA) is a significant predictor of peak relative strain. However, injury risk between individuals is not
easily delineated because of the large degree of variation in this trait. We hypothesize that the natural variation
in ACL CSA is accompanied by coordinated changes in tissue-level mechanical properties and/or other gross
anatomical features that together allow the ‘ACL-complex’ (i.e. the ligament and its entheses) to be
mechanically functional under routine loading conditions. We further hypothesize that this coordination,
although effective in establishing the strength of the ACL-complex, may result in changes in tissue-level
mechanical properties that deleteriously affect the fatigue resistance of the ACL-complex for certain
individuals. We will test our hypotheses using a mouse model that mirrors the natural variation in ACL-complex
traits among humans. At the completion of this work we will have an established mouse model for generating
new hypotheses, along with a better understanding of how the ACL-complex develops postnatally and
functionally adapts to mechanical loads. These outcomes are expected to guide interventions aimed at
maximizing ACL strength while minimizing ACL rupture among children and adolescents, and to have a broad
positive impact in other anatomically unique locations where ligamentous and tendinous injuries routinely occur
(e.g. rotator cuff, elbow, spine) and are likely influenced by a similar complex adaptive system wherein multiple
traits are coordinated to establish organ-level strength and stiffness.

## Key facts

- **NIH application ID:** 10231086
- **Project number:** 5R00AR070903-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Stephen Schlecht
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,512
- **Award type:** 5
- **Project period:** 2017-06-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231086

## Citation

> US National Institutes of Health, RePORTER application 10231086, Natural Variation in the Growth and Development of the ACL Complex (5R00AR070903-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10231086. Licensed CC0.

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