Thesis Defense: Alexander Drake Cigan

Nutrient Channels to Aid the Growth of Articular Surface-Sized Engineered Cartilage Constructs

Sponsor: Prof. Gerard Ateshian

Date & Time: Thursday, April 7th @ 10am
Location: Biomedical Engineering Conference Room (ET 353)
Osteoarthritis is a joint disease associated with the irreversible breakdown of articular cartilage in joints, resulting in pain and impaired mobility in many millions of patients worldwide and imposing substantial economic burdens. Cartilage tissue engineering strategies can produce cell-scaffold constructs at small sizes (< 5 mm diameter) with favorable functional properties, but due to transport limitations they cannot produce cartilage of sufficient size to treat severe arthritis. The inclusion of nutrient channels in constructs can mitigate these transport limitations by reducing path lengths to the construct center. In this dissertation we staged experiments cultivating channeled, bovine chondrocyte-seeded agarose constructs of increasing size, supported by theoretical predictions from system-specific computational models of nutrient transport and tissue growth. By designing and optimizing a culture system for channeled constructs, we successfully cultivated constructs the size of entire human knee cartilage surfaces, corresponding to a 10,000% increase in their former scale without compromising their functional properties. These are the largest ever constructs to possess native cartilage levels of compressive stiffness and proteoglycan content, and they demonstrate that channels are a highly effective technique for overcoming nutrient transport limitations and growing articular surface-sized cartilage to treat osteoarthritis.

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