Purpose: Meniscal injury and loss of meniscus tissue lead to osteoarthritis development. Therefore, novel biologic strategies are needed to enhance meniscus tissue repair. The purpose of this study was to identify a favorable culture medium for both bone marrow-derived mesenchymal stem cells (MSCs) and meniscal tissue, and to establish a novel meniscus tissue defect model that could be utilized for in vitro screening of biologics to promote meniscus repair.Materials and Methods: In parallel, we analyzed the biochemical properties of MSC - seeded meniscus-derived matrix (MDM) scaffolds and meniscus repair model explants cultured in different combinations of serum, dexamethasone (Dex), and TGF-β. Next, we combined meniscus tissue and MSC-seeded MDM scaffolds into a novel meniscus tissue defect model to evaluate the effects of chondrogenic and meniscal media on the tissue biochemical properties and repair strength.Results: Serum-free medium containing TGF-β and Dex was the most promising formulation for experiments with MSC-seeded scaffolds, whereas serum-containing medium was the most effective for meniscus tissue composition and integrative repair. When meniscus tissue and MSC-seeded MDM scaffolds were combined into a defect model, the chondrogenic medium (serum-free with TGF-β and Dex) enhanced the production of proteoglycans and promoted integrative repair of meniscus tissue. As well, cross-linked scaffolds improved repair over the MDM slurry.Conclusions: The meniscal tissue defect model established in this paper can be used to perform in vitro screening to identify and optimize biological treatments to enhance meniscus tissue repair prior to conducting preclinical animal studies.