Functional tissue engineering of chondral and osteochondral constructs

摘要

Due to the prevalence of osteoaithiitis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, theie is a great demand for an articular cartilage substitute As the bearing material of diarthiodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long-term culture environment, one can enhance the development of mechanical properties in chondrocyte-seeded agarose constructs As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate These osteochondral constructs develop cartilage-like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic defbrmational loading The results of these models suggest that while chondral ("gel alone") constructs see a largely homogenous field of mechanical signals, osteochondral ("gel bone") constructs see a largely inhomogeneous distribution of mechanical signals Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute.