Biomechanical Regulation of Architecture of Engineered Cartilage

University Of California-San Diego, La Jolla CA

Investigators

Abstract

9987353 Sah There is a need to extend the scientific basis for synthesizing articular cartilage tissue for treating arthritic joints. Current approaches have been unable to produce tissue with the functional architecture and biomechanical properties of normal articular cartilage. Such tissue is necessary for the repair of large articular defects or replacement of damaged joint surfaces. Previously, we and others have found that cartilaginous constructs, formed using current tissue- engineering approaches, can contain the major components of normal cartilage; however, the overall matrix density and mechanical properties of such constructs are markedly inferior to those of normal cartilage. Recently we found in short-term experiments that certain strain and fluid-flow stimuli regulate the synthesis and loss of matrix components from such constructs. Our other studies have experimentally measured and theoretically analyzed the depth-varying biomechanical properties of normal articular cartilage. Based on these results, we hypothesize that application of certain dynamic mechanical stimuli to growing cartilage constructs will induce formation of a tissue that resembles normal articular cartilage in composition, structure, and function. Further, we hypothesize that the mechanism of this will be through modulation of the synthesis and loss of specific tissue components in a spatially-varying manner. The specific aims of the proposed study will be conducted on engineered cartilage tissue. We will determine (1) how the density of seeded cells affects tissue thickness, mechanical function, and composition, (2) how long-term dynamic loading protocols, chosen to induce specific strain and fluid flow profiles, modulate the evolution of overall and depth-varying tissue function and composition, and (3) if this evolution can be explained by overall and depth-varying regulation of synthesis and loss of specific tissue components. The proposed work will emphasize quantitative experiments and analysis in the context of practical models for cartilage tissue engineering. During the course of the study, human resources will be developed for tissue engineering through the training of two graduate students.