Cellular and Chemical Gradients to Engineer the Meniscus‐to‐Bone Insertion

: Tissue-engineered menisci hold promise as an alternative to allograft procedures but require a means of robust fixation to the native bone. The insertion of the meniscus into bone is critical for meniscal function and inclusion of a soft tissue-to-bone interface in a tissue engineered implant can aid in the fixation process. The native insertion is characterized by gradients in composition, tissue architecture, and cellular phenotype, which are all difficult to replicate. In this study, a soft tissue-to-bone interface is tissue engineered with a cellular gradient of fibrochondrocytes and mesenchymal stem cells and subjected to a biochemical gradient through a custom media diffusion bioreactor. These constructs, consisting of interpenetrating collagen and boney regions, display improved mechanical performance and collagen organization compared to controls without a cellular or chemical gradient. Media gradient exposure produces morphological features in the constructs that appear similar to the native tissue. Collectively, these data show that cellular and biochemical gradients improve integration between collagen and bone in a tissue engineered soft tissue-to-bone construct.