Transection of the medial meniscus anterior horn results in cartilage degeneration and meniscus remodeling in a large animal model

Abstract

The meniscus plays a central load‐bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM). However, few large animal models of DMM exist and the joint‐wide initiation of the disease has not yet been defined in these models. Thus, the goal of this study is to develop and validate a large animal model of surgically induced DMM and to use multimodal (mechanical, histological, and magnetic resonance imaging) and multiscale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in 13 Yucatan minipigs. One month after DMM, joint contact area decreased and peak pressure increased, indicating altered load transmission as a result of meniscus destabilization. By 3 months, the joint had adapted to the injury and load transmission patterns were restored to baseline, likely due to the formation and maturation of a fibrovascular scar at the anterior aspect of the meniscus. Despite this, we found a decrease in the indentation modulus of the tibial cartilage and an increase in cartilage histopathology scores at 1 month compared to sham‐operated animals; these deleterious changes persisted through 3 months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to sham menisci at both 1 and 3 months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provide a new large animal testbed in which to evaluate therapeutics and interventions to treat post‐traumatic OA that originates from a meniscal injury.

Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model

“…Experimental conditions included an arthroscopic sham control (sham group; n = 5 at 1 month, n = 6 at 3 months, n = 5 at 6 months), a vertical longitudinal defect approximately 4 to 5 mm (vertical group; n = 6 at 1 month, n = 7 at 3 months, n = 4 at 6 months), and DMM 26 (DMM group; n = 6 at 1 month, n = 7 at 3 months, n = 5 at 6 months) and were randomized across stifle joints ( Table 1 ). Data from a subset (sham and DMM, 1- and 3-month time points) of these animals have been previously reported 6 and were used to establish the model system.…”

“… a DMM, destabilization of the medial meniscus. b Data previously published in part (Bansal et al 6 ). …”

“…Arthroscopic sham and DMM surgeries were performed as reported previously. 6 Briefly, a No. 11 scalpel blade was used to create lateral and medial parapatellar vertical 2-cm skin incisions, and sterile lactated Ringer solution was used to insufflate the joint.…”

“…DMM was performed via a complete transection of the anterior horn of the medical meniscus 26 with a No. 11 scalpel blade 6 ( Figure 1D and Supplemental Video 2). To confirm DMM, a probe was used to confirm that the attachment was fully detached.…”

“…After the animals were euthanized, the intact hindlimbs were removed, skin and excess musculature of the thigh were dissected away, and samples were hydrated in pads soaked with phosphate-buffered saline (PBS). Magnetic resonance imaging (MRI) scanning was carried out as previously described 6 using high-resolution T 1 volumetric interpolated breath-hold examination (VIBE) and multislice-multiecho (MSME) T 2 -weighted mapping sequences, 52 with a 30- to 35-minute total scan time. T 2 relaxation time was quantified in the anterior and posterior horns of the medial meniscus and the cartilage-cartilage and cartilage-meniscus contact areas of the medial tibial plateau, as described previously.…”