Negative printing for the creation of osteochondral scaffolds

An osteochondral (OC) defect is typically characterized by the loss of the full thickness of articular cartilage and any degree of the underlying subchondral bone. An OC defect can occur in a range of joints including the hip, shoulder, heel, and knee but this PhD project will focus only on defects of the knee. OC defects have been found in up to 20.8% of all knee arthroscopies, demonstrating the commonality of such a condition. The main components of the OC tissue are the articular cartilage and subchondral bone while there is a third component that lies between and has properties intermediate to the two (calcified cartilage). Cartilage is an avascular tissue with little to no ability to spontaneously heal. While instead, the subchondral bone has a vasculature network which provides access to a range of factors and cells, including immune cells, which provide a limited ability to self-repair small defects (<2.5 cm2). A defect within the OC tissue can lead to the accelerated breakdown of the surrounding tissue which can cause osteoarthritis. One symptom of osteoarthritis is the breakdown of the cartilage layer, with joints that can no longer move with ease, causing pain and reduced mobility. As such, it is important to repair the lost tissue with new tissue of a similar composition to the native. This PhD project explores the development of a novel treatment of OC defects, focusing exclusively on the articular cartilage and subchondral bone regions of the OC tissue. Each region is considered separately for the creation of implantable biological scaffolds. These are designed in silico to match the mechanical properties of their native tissue, while still allowing cells to generate new tissue. Specifically, a new 3D fabrication technique is created which can subsequently be used in all OC regions to create a bulk reinforcement structure. The scaffold design, cell type, additives and culture conditions, are then tailored to the needs of each separate region. In vitro and in ovo assays are used to test the chondro and osteo potential of the individual units. The result are cartilage and subchondral bone regeneration scaffolds which in future works can be combined to create a full OC scaffold.