Hydrodynamic Parameters Modulate Biochemical,Histological,and Mechanical Properties of Engineered Cartilage

Abstract

Functional engineered cartilage constructs represent a promising therapeutic approach for the replacement of damaged articular cartilage. The in vitro generation of cartilage tissue suitable for repair requires an understanding of the complex interrelationships between environmental cues, such as hydrodynamic forces, and tissue growth and development. In the present study, engineered cartilage constructs were cultivated in four well-defined hydrodynamic environments within a bioreactor, and correlations were established between construct ultrastructural and mechanical properties and key hydrodynamic parameters. Results suggest that even for similar composition, constructs may exhibit different mechanical properties due to differences in their ultrastructure that can be modulated by hydrodynamic parameters. For example, improved mechanical properties were observed in constructs that exhibited a thick fibrous outer capsule as a result of cultivation under increased hydrodynamic shear. In particular, uniformity in the contribution of the fluid velocity vectors (axial, radial, and tangential) to the total fluid velocity and shear stress were the hydrodynamic parameters that most affected the construct properties under investigation. The correlations identified here may be useful in the development of engineered tissue growth models that inform the design of bioreactor cultivation systems toward the production of clinically relevant engineered cartilage.