Summary

In this study, we have provided evidence that an electrospun nanofibrous scaffold combined with a mesenchymal stem cell-derived tissue engineered construct facilitated meniscal repair in a rabbit meniscal defect model, with implied repair of the meniscal hoop structure and with evidence for a subsequent chondroprotective effect.

Abstract

Damage to the meniscal hoop structure results in loss of biomechanical function, which potentially leads to the extrusion of the meniscus from the weight bearing area. However, there have been no established, effective treatments for such injuries. Previously, we have demonstrated that wrapping the radial tear with a cell-seeded aligned poly(e-caprolactone) (PCL) nanofiber scaffold fabricated by electrospinning enhanced meniscal radial tear repair based on both histological and biomechanical analyses, using a clinically relevant in vitro bovine meniscal explant model. The purpose of this study was to investigate the applicability of cell-seeded nanofibrous scaffolds to repair the damaged meniscal hoop structure along with the prevention of subsequent cartilage degeneration using a rabbit model.
Meniscal radial defects (5 mm width) in the medial meniscus were treated by wrapping and suturing with either an aligned electrospun nanofibrous scaffold alone (scaffold group, N=12) or a scaffold combined with a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs), (TEC-scaffold group, N=12), with the scaffold fiber direction matching that of the meniscal circumferential fibers. In the control group (N=12), no treatment was applied to the meniscal defect. Animals were randomly selected and euthanized under anesthesia at 4, 8, or 12 weeks after implant surgery. The distal femur and medial menisci of animals were used for histological analysis. As an evaluation of meniscal hoop function, the ratio of meniscal uncovered area on the medial tibial plateau is calculated, since it would be difficult to precisely measure the meniscal extrusion in small animals.
Histologically, the articular cartilage on the medial femoral condyles of both the control and scaffold group animals showed evidence for accelerated development of osteoarthritis-like changes with a loss of matrix staining with Safranin O. Conversely, the TEC-scaffold group maintained the integrity of the structure of the hyaline cartilage with findings for strong matrix staining with Safranin O until 12 weeks after surgery. The meniscal uncovered area on the medial tibial plateau at 12 weeks was significantly higher than those at 4 weeks for both the control or scaffold alone groups. Notably, such areas for the TEC-scaffold group did not become statistically worse with time, suggesting repair and stabilization of hoop structure integrity over time. Also, meniscal defects treated with such TEC-combined nanofibrous scaffolds were consistently repaired with a fibrocartilaginous tissue with positive staining for Safranin O in the inner zone of meniscus.
In this study, we have provided evidence that an electrospun nanofibrous scaffold combined with an MSC-derived TEC facilitated meniscal repair in a rabbit meniscal defect model, with implied repair of the meniscal hoop structure and with evidence for a subsequent chondroprotective effect. The present technique to repair damaged meniscal hoop structure integrity could contribute to the development of a new meniscal repair technique for a disruption of hoop fibers (e.g., radial tear) with potential for high clinical relevance.