TISSUE ENGINEERING THE MENISCUS FOR CLINICAL TRANSLATION: STEM CELLS, FIBERS, AND ATTACHMENTS
McCorry, Mary Clare
In the United States, there are over 1 million meniscus related surgeries per year. Meniscus injury is often caused by trauma or overuse. The best treatment option for extensive meniscal degeneration or loss is allograft replacement, however, allograft availability is limited by immunological and anatomical constraints. This work aims to develop a tissue-engineered meniscus that eliminates these constraints by using the patient’s own cells and the exact anatomical shape. In order for tissue engineered menisci to become a viable treatment alternative, several pre-clinical challenges must be addressed (Chapter 1). Mesenchymal stem cells (MSCs) are a promising clinically available cell source. Co-culture with the native cell type was evaluated as a technique to guide fibrochondrogenic differentiation (Chapter 3). The development of large diameter and organized collagen fibers is essential to mechanical stability of a tissue engineered meniscus. The ability of MSCs to form fibers in mono and co-culture was evaluated (Chapter 4) as well as addition of glucose as a technique to improve fiber formation was explored (Chapter 5). Engineering soft tissue to bone interfaces with appropriate mechanical, chemical, and cellular gradients is essential for the long term stability of an implant, however this presents unique tissue engineering design challenges (Chapter 2). A model system was developed to run high throughput experiments targeted at designing meniscal entheses for surgical fixation of tissue engineered constructs (Chapter 6).
Collagen; Enthesis; Meniscus; Mesenchymal Stem Cell; Proteoglycan; Biomedical engineering; Tissue Engineering
Maher, Suzanne A.; Fortier, Lisa Ann; Estroff, Lara A.
PHD of Biomedical Engineering
Doctor of Philosophy
dissertation or thesis