EFFECTS OF MEDIA STIRRING AND PRESENCE OF NUTRIENT CHANNELS ON FUNCTIONAL PROPERTIES OF LARGE ENGINEERED CARTILAGE CONSTRUCTS

摘要

Cartilage tissue engineering is a promising approach for the replacement of degraded joint cartilage in osteoarthritis (OA) patients. Current strategies employ smaller constructs (～20mm~2), however OA generally does not become symptomatic until defects reach ≥ 5 cm~2. Therefore, small constructs may not ultimately be clinically relevant for treatment of OA. Attempts to scale up construct size are met with challenges, as inhomogeneous properties develop as a result of poor nutrient availability at the construct center due to cellular consumption at the periphery. Previously, the incorporation of Ø1 mm nutrient channels in large (Ø10 mm) constructs was found to improve Young's modulus (E_y) and glycosaminoglycan (GAG) content and reproduce their native values. Rotational mixing has been shown to improve properties of micro-channeled constructs. As a major goal of our research is to optimize channel size and arrangement to improve the quality of large engineered cartilage constructs, it is essential to develop a simple but effective method for convecting media through channeled constructs. Therefore, this study seeks to compare the functional properties of large constructs that are subjected to different types of media stirring, by rocking or orbital motion, and to determine whether either of these conditions favors the quality of constructs with nutrient channels.