Critical-sized cartilage defects in the equine carpus

ABSTRACT

Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and µCT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 ± 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T_1Gd). Larger chondral defects showed poor filling (50.6 ± 2.7% in 4 mm and 31.9 ± 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 ± 3.0%, 68.0 ± 4.6% and 70.8 ± 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.

KEYWORDS:

• Animal model
• cartilage repair
• critical-sized defect
• preclinical research
• spontaneous repair

Acknowledgments

The authors wish to thank Outi Kiekara (Department of Anatomy, University of Eastern Finland, Kuopio, Finland) for µCT and MR imaging. We thank Nora Rauhala (Department of Applied Physics, University of Eastern Finland, Kuopio, Finland) for conducting the ROI analyses on the MRI data and Eija Rahunen (Department of Anatomy, University of Eastern Finland, Kuopio, Finland) for technical assistance with histological sample preparation. The Biomedicum Imaging Unit (Faculty of Medicine, University of Helsinki) is acknowledged for microscopy services and Hannu Kautiainen (Medcare Oy, Äänekoski, Finland) for the statistical analyses.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This study was funded by the Academy of Finland (Grant #285909) and the Finnish Funding Agency for Innovation Tekes (Grant 3344/31/03). The funding sources had no role in the study design, collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.