Allograft Derived Bioscaffolds for Tissue Engineering of the Meniscus: An in vivo Ovine Study and the Effect of Hypoxic Culture on Seeded Meniscus Constructs

The meniscus is a fibrocartilagenous wedge shaped semilunar tissue that plays an important role in knee joint function and stability. The structure of the meniscus is integral to its function as it provides protection and cushion to the knee joint. Irreparable meniscus tears and meniscus degeneration contribute to the development of osteoarthritis of the knee joint. Current medical interventions to treat meniscus injury are limited to attempts at surgical repair or resection through partial or total meniscectomy. Significant loss or dysfunction of the meniscus as a result of injury or partial meniscectomy alters the mechanics of the knee and contributes to the development of degenerative joint disease, pain, and disability. Allograft meniscus replacement has been shown to decrease the pain associated with meniscus deficiency. However, this procedure still has significant limitations that have been linked to incomplete cellular incorporation, microscopic immune response, and limited long-term durability of these constructs. To overcome these limitations, this work investigated the use of a natural bioscaffold to mimic natural tissue architecture and biomechanical properties. These tissue engineered scaffolds were tested in an in vivo ovine meniscectomy model to determine their chondroprotective ability. These scaffolds were also used in in vitro culture under hypoxic conditions for the differentiation of mesenchymal stem cells toward a fibrochondrocyte phenotype. This work showed that meniscus scaffolds and cell seeded constructs maintained their gross structure and position when implanted into ovine stifle joints for six months. While complete tissue integration was not achieved, proteoglycan staining and extra cellular matrix (ECM) remodeling was observed in the area of tissue healing. In addition, this work demonstrated the use of an in vitro three-dimensional culture system for the attachment and migration of cells for differentiation under normal culture conditions.