Repairing Damaged Cartilage
The Cellular Engineering laboratory, directed by Prof. Clark Hung, is undertaking studies to establish methods of repairing damaged articular cartilage in various joints of the human body.
Cartilage damage can take the form of focal defects and denudation of the articular surface. Recent approaches at therapy have been to fill these defects with cell-embedded scaffolds in the hope that the cells will produce an extracellular matrix with the same functional properties as healthy cartilage. The cell scaffolds are made from a variety of biocompatible materials and come in various shapes, including pre-made cylindrical plugs and in-situ gelatinous injections. A major concern with this technique, however, is the quality of integration of the newly formed cartilage with its surrounding tissue. Cartilage plugs, whether in the form of autologous explants or tissue-engineered constructs, do not adhere well to the smooth, well-lubricated walls of healthy cartilage. These incongruencies may lead to anomalies in fluid flow and stress distribution within the joint. Similar problems may also arise if the precise geometry of the articular surface is not maintained; for example, if a cylindrical plug with a flat top was inserted into a defect that had a smooth, sloping surface.
To address these concerns the lab is developing techniques to reproduce the entire articular surface of healthy joints. Anatomically correct molds of the patellar and carpometacarpal (CMC) cartilages are produced using either SPG or MRI data. These molds are patient-specific and closely reproduce the original contours of the joints. Cell-laden agarose constructs are then produced which accumulate an extracellular matrix, develop better material properties, and maintain a distinct geometry over a five-week culture period. This is a first step in demonstrating the feasibility of producing anatomically correct, joint specific constructs for the replacement of load bearing cartilage. To be considered successful, however, the material properties of the construct have to be greatly improved and a method of incorporating the construct into the underlying bone has to be developed.
Research done in the lab and by other groups has shown that the application of dynamic strain to cell-laden agarose constructs increases the resulting tissue properties. Ongoing studies with with cylindrical specimens are aimed at refining this loading protocol. Based on these studies, a bioreactor was deveoloped that can dynamically load the joint specific constructs as a whole.
Several different approaches are being pursued to address the issue of attachment and incorporation of the construct to the underlying bone. Although cartilage does not adhere well to itself, bone attaches very well to bone, as evidenced by healing fractures and other bone-level injuries. One promising approach therefore is to produce bi-layered constructs composed of an agarose layer and a devitalized bone layer. The resulting osteochondral construct would be mechanically and biochemical stimulated to produce functional tissue properties and would then be inserted into an osteochondral defect. An alternative approach is to produce composites with sintered PGLA micro spheres. These micro spheres are biodegradable and avoid potential problems inherent in using bone such as availability and disease transmission.
In summary, the lab hopes that by creating bi-layered tissue constructs with the proper surface geometry and a suitable base, the replacement of entire joint surfaces in a patient-specific manner can be considered, solving the problem of congruence and integration.