Tissue-Engineered Osteochondral Allograft Versus Fresh Osteochondral Allograft: Comparable Cartilage and Subchondral Bone Repair in a 14-Month Equine Osteochondral Defect Model

Abstract

Background:

Fresh osteochondral allograft (OCA) transplantation effectively repairs cartilage and subchondral bone; however, the persisting shortage of available donor OCAs and their short shelf-life make scheduling surgeries and meeting patient demand challenging. Attempts have been made to develop tissue-engineered solutions to address the limitations of OCA; nonetheless, these have failed to progress beyond the preclinical stage.

Purpose:

To assess the safety and efficacy of a tissue-engineered osteochondral allograft (TE-OCA) as compared with equine OCA in an equine osteochondral defect model.

Study Design:

Controlled laboratory study.

Methods:

Bilateral critical-size (10 × 7.0-7.5 mm) osteochondral defects were surgically created on the femoral medial trochlear ridge of healthy, skeletally mature horses (2-5 years; n = 8). A TE-OCA was placed into 1 defect, and an OCA was placed into the contralateral defect as a positive control. At surgery, throughout the study, and at sacrifice (14 months), quantitative evaluation of lameness and synovial fluid composition was obtained, while radiographs, arthroscopies (4, 10, and 12 months), or gross images, and synovial membrane were qualitatively scored. Postmortem, joints and grafts were evaluated using T1- and T2-weighted magnetic resonance imaging, quantitative computed tomography, and biomechanical testing. Histology and immunohistochemistry were performed on osteochondral blocks that were qualitatively scored.

Results:

TE-OCA exhibited better cartilage-cartilage integration on histology (97.1 ± 7.6 vs 41.7 ± 45; P = .03) and a lower T1ρ quantitative score (65.6 ± 10.6 vs 72.8 ± 5.5; P = .03) than OCA, indicative of an intact regeneration of cartilage matrix. TE-OCA matured in vivo, with biomechanical instantaneous and equilibrium compressive moduli improving to match that of OCA (1.74 ± 0.7 vs 1.96 ± 1.2 MPa [P≥.999], and 0.39 ± 0.2 vs 0.18 ± 0.2 MPa [P = .22], respectively). There were no differences between total radiographic scores (3.6 ± 2.7 vs 2.1 ± 1.7; P = .9), total International Cartilage Repair Society cartilage scores (5.1 ± 4.9 vs 2.8 ± 0.8; P = .6), and total morphologic MRI scores (8.9 ± 2.8 vs 6.2 ± 3.7; P = .3) at the study end. No off-target effects were seen.

Conclusion:

TE-OCA is comparable to OCA in multiple safety and efficacy measures of osteochondral defect repair.

Clinical Relevance:

This preclinical study indicates that TE-OCA provides an alternative solution to OCA and addresses the long-standing issues of limited supply and short shelf-life.