A novel Tissue Engineering Approach for Meniscus Replacement Evaluated Utilising an Ovine Explant Model

Abstract

Purpose - Allografts and synthetic scaffolds made from a proprietary mix of polyurethane and poly-caprolactone (Actifit®) are used clinically as meniscus replacement strategies. Both approaches have shown limited success. The purpose of this study is to assess whether the introduction of autologous cells to commercial scaffolds using a fibrin gel delivery system might improve the synthetic meniscus approach.

Methods and Materials - Medial and lateral menisci were harvested from n=5 sheep. Medial menisci were used to isolate meniscal cells from the avascular region, whilst punch defects (3mm) were created in lateral menisci and cylinders of Actifit® were inserted. Culture expanded avascular meniscal cells with progenitor characteristics were seeded into scaffolds with or without fibrin gel (including an acellular control). The explants were cultured in vitro for 28 days, after which GAG and DNA content were assessed, as well as type I collagen via immunohistochemistry.

Results - Fibrin gel retained cells within the scaffolds and no detachment was observed between the meniscus tissue and scaffold at day 28. In contrast, in the cells without fibrin group, cells were observed streaming out of the scaffold onto plastic and meniscus tissue and scaffold detachment was observed at day 28. GAG and DNA analysis both showed that scaffolds with cells delivered by fibrin gel had higher values for both, compared to the cell only group (figure 1). Histological evaluation confirmed the presence of more collagen I in the fibrin and cells group.

Conclusion - We have demonstrated the feasibility of using fibrin gel to deliver autologous meniscal progenitor cells from the avascular region into a clinical grade meniscus substitute in vitro. Cells delivered by fibrin gel showed increased retention and matrix production within the scaffold compared to cells directly seeded into the scaffold without fibrin. Our data is encouraging for the further development of a novel cell-based tissue engineering approach for meniscus replacement in the clinic.

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