Development of engineered menisci with native-like organization using high density collagen gels and mechanical stimulation

Meniscal injuries are one of the most common traumatic injuries in the knee accounting for over 1 million surgeries a year in the United States. Treatment of meniscus lesions is the most frequent procedure carried out by orthopaedic surgeons, and while there have been advances in partial repair strategies, improvements are still needed for whole meniscal replacement. Currently, the only treatment for total meniscal replacement is meniscectomy followed by cadaveric allograft, which is applicable in only a small percentage of patients, demonstrating the potential for a tissue engineered meniscus.

The focus of this dissertation was to investigate the effect of mechanical stimulation, chemical stimulation, and material choice on the development of tissue engineered menisci. The goal was to move toward a viable whole meniscus replacement. The completion of this body of work resulted in the development of an anatomical meniscal construct with native-like organization, equilibrium modulus, and anisotropic tensile properties. First, mechanical and chemical stimulation was found to significantly improve biochemical and mechanical properties of alginate menisci (Chapters 3 and 4). Next, high density type I collagen gels were investigated as a potential new scaffold choice and were found to be superior to alginate menisci (Chapter 5). Finally, mechanical stimulation was used to guide native-like organization in high density collagen menisci. Culturing with biomimetic horn-anchored boundary conditions produced scaffolds with native-like circumferential and radial fiber organization, and development of anisotropic mechanical properties (Chapter 6). These horn-anchored conditions were then combined with compressive loading to investigate the effect of a bioreactor capable of applying physiological loading patterns (Chapter 7). This compressive-tensile loading regime accelerated the development of collagen menisci and improved all fibrocartilage properties.

This work has been at the forefront of a paradigm shift in the field to capture native organization, which is believed to be fundamental to meniscal load distribution in vivo. These are some of the most organized meniscal scaffolds produced to date and demonstrate great promise as meniscal replacements. This work establishes the potential of collagen constructs as meniscal replacements and presents many new research directions while providing the platform necessary to move toward clinical meniscal replacements.