Arthroscopic surgery for meniscus injury, degenerative or acute, is one of the most common surgical procedures performed by orthopaedic surgeons. Irreparable meniscus tears and meniscus degeneration contribute to the development of osteoarthritis of the knee joint. Current medical interventions to treat meniscus pathology are limited to attempts at surgical repair or resection through partial or total meniscectomy. Allograft meniscus replacement has been shown to decrease the pain associated with meniscus deficiency. The limitations of the clinical success of allograft meniscus replacement have been linked to incomplete host cellular incorporation, host immune response, and limited long term viability of these constructs. The long-term objective of this project is to create a mesenchymal stem cell (MSC) seeded porous meniscus bioscaffold that is viable, promotes matrix remodeling, and is durable. The goal of this proposal is to determine the oxygen tension and mechanical stimulation parameters necessary to cultivate a viable meniscus transplant construct and compare it to healthy native meniscus tissue. The central hypothesis of this proposal is that exposure of seeded scaffolds to the lowered oxygen tension and compressive mechanical loading forces similar to in vivo joint conditions will support extracellular matrix (ECM) production, cellular homeostasis and viability parameters similar to normal intact meniscus tissue. In order to test this hypothesis, the following specific aims will be performed: 1) Characterize the ECM and cells obtained from inner and outer regions of fresh meniscus tissue and primary cell culture to define a set of ideal tissue engineering outcome parameters based on normal intact human meniscus tissue. 2) lnvestigate the effect of hypoxia growth conditions on human MSC seeded scaffold viability, ECM production, and mechanical properties using a three dimensional tissue plug bioreactor model. 3) Examine the effect of dynamic mechanical compression on human MSC seeded scaffold viability, ECM production and mechanical properties in a three dimensional tissue plug bioreactor model. Irreparable meniscus tears and meniscus degeneration contribute to the development of osteoarthritis of the knee joint. Current medical interventions to treat meniscus tears are limited to surgical repair and tissue transplantation. Meniscus transplants have been shown to decrease pain, but have limited success rates. The objective of this proposal is to produce a more viable meniscus transplant.
