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Validation of Porcine Knee as a Sex-specific Model to Study Human Anterior Cruciate Ligament Disorders

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated.

Questions/purposes

We asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury.

Methods

Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90° flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees.

Results

Female pigs had smaller bicondylar widths (2.9 mm, ratio = 0.93, effect size = −1.5) and intercondylar notches (width: 2.0 mm, ratio = 0.79, effect size = −2.8; area: 30.8 mm2, ratio = 0.76, effect size = −2.1; index: 0.4, ratio = 0.84, effect size = −2.0), steeper lateral tibial slope (4.3°, ratio = 1.13, effect size = 1.1), smaller ACL (length: 2.7 mm, ratio = 0.91, effect size = −1.1; area: 6.8 mm2, ratio = 0.74, effect size = −1.5; volume: 266.2 mm3, ratio = 0.68, effect size = −1.5), thinner medial femoral cartilage (0.4 mm, ratio = 0.8, effect size = −1.1), lower ACL yield load (275 N, ratio = 0.81, effect size = −1.1), and greater AP knee laxity at 30° (0.7 mm, ratio = 1.32, effect size = 1.1) and 90° (0.5 mm, ratio = 1.24, effect size = 1.1) flexion compared with their male counterparts. These differences were significant for all parameters (p ≤ 0.04). Observed sex-related differences were similar to those reported for the human knee.

Conclusions

Significant differences exist between knees of male and female pigs with respect to prominent anatomic and biomechanical factors. Our findings strongly agreed with published data regarding human knees.

Clinical Relevance

The findings highlight the use of the porcine large animal model to study the role of sex on ACL injuries and surgical outcome. This validated preclinical model may facilitate the development of novel, sex-specific interventions to prevent and treat ACL injuries for male and female patients.

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Acknowledgments

We thank Patrick Vavken MD (Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School) and Benedikt Proffen MD (Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School) for helping with surgical procedures, Alison Biercevics BS (Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital) for assistance with MRI, and David Paller MS (Rhode Island Hospital Orthopaedic Foundation), Sarath Koruprolu BS (Rhode Island Hospital Orthopaedic Foundation), and Ryan Rich BS (Rhode Island Hospital Orthopaedic Foundation) for assistance with mechanical testing.

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Authors and Affiliations

  1. Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA

    Ata M. Kiapour PhD & Martha M. Murray MD

  2. Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, RI, USA

    Matthew R. Shalvoy BS & Braden C. Fleming PhD

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  1. Ata M. Kiapour PhD
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  2. Matthew R. Shalvoy BS
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  4. Braden C. Fleming PhD
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Corresponding author

Correspondence to Martha M. Murray MD.

Additional information

Funding for this study was (MMM and BCF) received from the National Institutes of Health (RO1-AR054099 [MMM], AR056834 [BCF and MMM], and P20 GM104937 [BCF] [Bioengineering Core]) and the Lucy Lippitt Endowment.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Clinical Orthopaedics and Related Research ® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA, and the Department of Orthopaedics, Rhode Island Hospital, Providence, RI, USA.

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Kiapour, A.M., Shalvoy, M.R., Murray, M.M. et al. Validation of Porcine Knee as a Sex-specific Model to Study Human Anterior Cruciate Ligament Disorders. Clin Orthop Relat Res 473, 639–650 (2015). https://doi.org/10.1007/s11999-014-3974-2

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