Mechanical properties of articular cartilage, including stiffness, biolubrication, and wear-resistance, undergo deterioration during progression of diseases such as osteoarthritis. When the tissue becomes softened and wear-prone, resulting from biochemical alterations within the cartilage matrix, osteoarthritis patients experience painful joint degeneration and erosion of the bone-protective cartilage. Moreover, the synovial fluid bathing the cartilage also experiences a reduction in lubricating capacity as osteoarthritis advances, further hastening wear. An existing treatment paradigm known as viscosupplementation, designed to restore a viscous and lubricating nature to the synovial fluid, involves intraarticular injection of hyaluronic acid into affected joints. While this technique relieves pain for some individuals, the majority of patients experience neither pain relief nor protection of the cartilage from further damage.
To address the unmet need of patients requiring chondroprotective thera-pies, this dissertation describes two potential intraarticular strategies based on the application of polymer chemistry principles to bodily tissues and interfaces. One strategy involves the synthesis of a non-hyaluronic-acid synovial fluid sup-plement, based on a phosphorylcholine-containing polyacrylate network, de-signed to functionally mimic the lubricity of the glycoprotein lubricin, phospho-lipid macromolecular assemblies, and high molecular weight hyaluronic acid. The second strategy involves the in situ photopolymerization of a related polyacrylate within cartilage bulk tissue to strengthen, prevent wear, and in-crease the proportion of compressive load supported by the tissue’s interstitial fluid rather than solid matrix. In this strategy, the branched polymer network functionally mimics the glycosaminoglycans that are found in healthy cartilage but depleted in osteoarthritic cartilage. For both potential therapies, chemical and physical properties of the respective fluid and tissue are analyzed, and ex vivo cartilage mechanical testing involving axial and shear deformation reveal the biotribological and compressive reinforcement conferred by the zwitterionic polymer. The synovial fluid supplement significantly decreases cartilage friction through a variety of lubrication mechanisms depending upon tissue fluid flow state and articulation conditions, and the cartilage-reinforcing supplement pro-tects cartilage during accelerated wear testing while also improving synovial flu-id’s ability to lubricate polymer-impregnated cartilage. The fundamental tissue—biomaterial tribological interactions investigated in this dissertation will inform the rational design of therapeutic, friction-reducing polymers for diverse applications. / 2019-04-04T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/21725 |
| Date | 04 April 2017 |
| Creators | Cooper, Benjamin Goldman |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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