Osteoarthritis (OA) is the most common form of arthritis, often thought of as a disease of the elderly, but post traumatic OA predominantly impacts younger individuals. Articular cartilage is the tissue that coats the end of your bones in synovial joints. Since cartilage has limited healing capacity, defects, or injuries to it progressively erodes down to the subchondral bone. Unfortunately, current treatment options all have limitations, particularly for younger patients. Cartilage has a specific zonal architecture that is distinguished by the different cell morphologies and arrangements, biochemical composition, and mechanical properties. 3D bioprinting is a tissue engineering technique that involves the simultaneous extrusion of biomaterials and cells to fabricate constructs. The layer-by-layer nature of 3D bioprinting and the frequent use of hydrogels as biomaterials make it a promising technique to engineer zonal articular cartilage. The goal of this dissertation was to develop and use novel human reporter chondrocytes to determine optimal combinations of biomaterials to 3D bioprint both the middle-deep and surface zones of articular cartilage. Human articular chondrocytes were transduced with either a type II collagen promoter- or lubricin promoter-driven Gaussia luciferase. Upon promoter stimulation, luciferase is secreted by the cells enabling a high-throughput, temporal, assessment of either type II collagen or lubricin. The human chondrocyte reporter system was combined with a Design of Experiment approach which streamlined the process of biomaterial optimization. To 3D bioprint the deep zone, an optimal combination of gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) was determined based on type II collagen promoter-driven luminescence, chondrocyte mobility and biomaterial stiffness. While an optimal combination of GelMA and oxidized methacrylated alginate (OMA) was determined for the surface zone based on lubricin promoter-driven luminescence, lubricin secretion, and construct shape fidelity. Together these results highlight the effectiveness of human reporter chondrocyte optimization for 3D bioprinting zonal cartilage.
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Doctor of Philosophy (Ph.D.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Martyniak, Kari, "Reporter Chondrocyte Optimization of Bioinks for Zonal 3D Bioprinting of Cartilage" (2022). Electronic Theses and Dissertations, 2020-. 1407.