Biomimetic Boundary Lubricants Of Articular Cartilage
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The glycoprotein lubricin is the primary boundary lubricant of articular cartilage. In injured joints, supplementation with lubricin prevents further damage. The lubricating and chrondroprotective abilities are believed to be linked. Furthermore, the lubricating abilities of lubricin are thought to arise from its structures. The C-terminus of lubricin binds the molecule to an articulating surface, and the hydrophilic oligosaccharide brush draws and traps water near the surface. These structures work in tandem to hydrate articulating surfaces, imparting lubrication and facilitating movement. Since this boundary lubricating mechanism is thought to arise from lubricin's structure, a series of poly(acryilic acid)-graft-polyethylene glycol (pAA-g-PEG) brush co-polymers were synthesized. The copolymers were equipped with a thiol terminus to bind them to surfaces much like the C-terminus of lubricin. By mimicking the hydrophilic, brush-like structure of lubricin, pAA-g-PEG copolymers were effective boundary lubricants of articular cartilage. Using different pAA backbone sizes and PEG side chain sizes, the lubricin-mimetics were tuned to create surfaces of different characteristics and different lubricating abilities. To tune their lubricating domain, pAA-g-PEG polymers were bound to gold surfaces by self-assembly via a terminal thiol. The pAA-g-PEG copolymers then effectively mimicked the structure and function of the cartilage lubricant lubricin. A library of eight polymers were synthesized with varying pAA iii backbone size, PEG side chain size, and PEG:AA side chain density. They bound to cartilage surfaces with binding time constants ranging from 20 to 41 min, and polymer binding was proportional to their lubricating ability. Six of the eight lubricin-mimetics effectively lubricated cartilage surfaces in vitro, with two mimetics lubricating more effectively than the lubricinmutant LUB:1. This work provides evidence supporting approaches to mitigate cartilage damage using boundary lubricants. The lubricin-mimetics created in this study mimic only lubricin's structure, yet demonstrated the ability to both lubricate and protect cartilage. This ability was manipulated by varying the size of the components of the mimetics, and more effective lubricants resulted in better preservation of the cartilage tissue in injured joints evident by both the preservation of the cartilage's lubricating surface and histologic OARSI scoring. Thus, lubricants that lubricate cartilage more effectively when administered in vitro can be used as a screening process to determine the lubricant's effectiveness at protecting cartilage in vivo and preventing injury and disease progression. iv
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Putnam, David A.