Article: Samaroo, KJ; Tan, M; Putnam, D; Bonassar, LJ; “Binding and Lubrication of Biomimetic Boundary Lubricants on Articular Cartilage”, Journal of Orthopaedic Research, 35 (3):548-557
Abstract: The glycoprotein, lubricin, is the primary boundary lubricant of articular cartilage and has been shown to prevent cartilage damage after joint injury. In this study, a library of eight bottle-brush copolymers were synthesized to mimic the structure and function of lubricin. Polyethylene glycol (PEG) grafted onto a polyacrylic acid (pAA) core mimicked the hydrophilic mucin-like domain of lubricin, and a thiol terminus anchored the polymers to cartilage surfaces much like lubricin’s C-terminus. These copolymers, abbreviated as pAA-g-PEG, rapidly bound to cartilage surfaces with binding time constants ranging from 20 to 39min, and affected lubrication under boundary mode conditions with coefficients of friction ranging from 0.140 +/- 0.024 to 0.248 +/- 0.030. Binding and lubrication were highly correlated (r(2)=0.89-0.99), showing that boundary lubrication in this case strongly depends on the binding of the lubricant to the surface. Along with time-dependent and dose-dependent behavior, lubrication and binding of the lubricin-mimetics also depended on copolymer structural parameters including pAA backbone length, PEG side chain length, and PEG:AA brush density. Polymers with larger backbone sizes, brush sizes, or brush densities took longer to bind (p<0.05). Six of the eight polymers reduced friction relative to denuded cartilage plugs (p<0.05), suggesting their potential to lubricate and protect cartilage in vivo. In copolymers with shorter pAA backbones, increasing hydrodynamic size inhibited lubrication (p<0.08), while the opposite was observed in copolymers with longer backbones (p<0.05). These polymers show similar in vitro lubricating efficacy as recombinant lubricins and as such have potential for in vivo treatment of post-traumatic osteoarthritis. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:548-557, 2017.
Funding Acknowledgement: NIH/NIAMS [1 R01 AR066667-01]; New York State Advanced Research Program (NYSTAR) [DMR-05220404]; SAGE Fellowship; Provost’s Diversity Fellowship; Morgan Fellowship; Cornell University Biotechnology Resource Center [NIH S10RR025502]
Funding Text: Grant sponsor: NIH/NIAMS; Grant number: 1 R01 AR066667-01; Grant sponsor: New York State Advanced Research Program (NYSTAR); Grant sponsor: DMR-05220404 Seed Grant; Grant sponsor: SAGE Fellowship; Grant sponsor: Provost’s Diversity Fellowship; Grant sponsor: Morgan Fellowship; Grant sponsor: Cornell University Biotechnology Resource Center; Grant number: NIH S10RR025502.