UC San Diego

Articular cartilage is a load-bearing tissue with a limited capacity for self-repair. One approach to cartilage repair is to use tissue engineered constructs to repair defects by replacement of the absent and damaged tissue. Current therapies only target focal defects and utilize chondrocytes from intact cartilage. In the case of larger defects, or an entire joint, a tissue engineered construct is a possible future therapeutic solution. Human chondrocytes from osteoarthritic (OA) knees are potentially an abundant cell source for creating large- scale human cartilaginous constructs. Another requirement for such constructs is attainment of mechanical function, which relates directly to the biochemical properties of the tissue. The application of a semi-permeable membrane can modulate the matrix content within the construct. The aims of this dissertation were to determine the utility of chondrocytes from OA knees as a cell source for large- scale human cartilage tissue engineering and the effects of a semi-permeable membrane on the matrix properties of cartilaginous constructs. Chondrocytes from OA cartilage were expanded with growth factors and serum to levels relevant to joint-scale cartilage tissue engineering. When chondrocytes were redifferentiated with human serum, they produced chondron-like structures and matrix molecules characteristic of native cartilage. Cohesive cartilaginous tissues were formed from these chondrocytes derived from OA cartilage. To study effect of a semi-permeable membrane on matrix properties, cartilaginous constructs were formed with calf chondrocytes in a perfusion bioreactor system. The content of matrix, in particular aggrecan, was dependent on membrane pore size and porosity, with larger amounts of matrix retained in the construct when a smaller pore size and lower porosity was utilized. A compartmental model was developed to describe the effects of the membrane on the distribution of matrix in the construct and culture medium. These studies demonstrate that chondrocytes from OA cartilage are a feasible cell source for human cartilage tissue engineering, and that a semi- permeable membrane can be used to modulate matrix content in cartilaginous constructs. For clinical applications, both methods could be implemented in concert, to create large-scale cartilaginous constructs with enhanced biochemical properties, and, ultimately, a treatment solution for resurfacing of damaged or OA joints