Boundary mode lubrication of articular cartilage with a biomimetic diblock copolymer

Abstract

We report the design of a diblock copolymer with architecture and function inspired by the lubricating glycoprotein lubricin. This diblock copolymer, synthesized by sequential reversible additionfragmentation chain-transfer polymerization, consists of a cationic cartilage-binding domain and a brush-lubricating domain. It reduces the coefficient of friction of articular cartilage under boundary mode conditions (0.088 ± 0.039) to a level equivalent to that provided by lubricin (0.093 ± 0.011). Additionally, both the EC 50 (0.404 mg/mL) and cartilage-binding time constant (7.19 min) of the polymer are comparable to purified human and recombinant lubricin. Like lubricin, the tribological properties of this polymer are dependent on molecular architecture. When the same monomer composition was evaluated either as an AB diblock copolymer or as a random copolymer, the diblock effectively lubricated cartilage under boundary mode conditions whereas the random copolymer did not. Additionally, the individual polymer blocks did not lubricate independently, and lubrication could be competitively inhibited with an excess of binding domain. This diblock copolymer is an example of a synthetic polymer with lubrication properties equal to lubricin under boundary mode conditions, suggesting its potential utility as a therapy for joint pathologies like osteoarthritis. lubricin | biomimetic | boundary mode lubrication | osteoarthritis

Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model

“…Structurally, these mimetics differed in their binding orientations and steric interactions while sharing common features, such as polyacrylic acid backbone size, polyethylene glycol brush size, and polyacrylic acid:polyethylene glycol brush density. 31,34 We found that the group 3 mimetic demonstrated the largest differences in OARSI score for femoral articular cartilage degeneration, suggesting that it may provide a degree of chondroprotection (P = .0445). This chondroprotective capacity of the group 3 lubricin mimetic versus its control was .…”

“…Structurally, these mimetics differed in their binding orientations and steric interactions while sharing common features, such as polyacrylic acid backbone size, polyethylene glycol brush size, and polyacrylic acid:polyethylene glycol brush density. 31,34…”

“…The 4 mimetics were synthesized to differ from one another with respect to their binding orientations and steric interactions ( Table 1). All polymers under study were synthesized in accordance with the methodology described by Sun et al 34 After the synthesis process, the 4 lubricin mimetic polymers under study were characterized through nuclear magnetic resonance spectroscopy with an Inova 400-MHz spectrometer with deuterated chloroform or deuterium oxide as the solvent.…”

Mega macromolecules as single molecule lubricants for hard and soft surfaces

“…For the natural soft surface, we selected articular cartilage for evaluation of the mega HPGs as lubrication of this surface is key for bodily movement, protection from wear, and prevention of osteoarthritis 10,[40][41][42][43][44] . Previously, linear 10,45 and brush polymers 40,46,47 have been explored for lubricating cartilage as these materials present controlled electrostatic interactions and hydration. Additionally, with the brush structures, the tilting and/ or the physical thinning of the polymer chains improves the lubricant properties 48,49 .…”

High Lubricity Meets Load Capacity: Cartilage Mimicking Bilayer Structure by Brushing Up Stiff Hydrogels from Subsurface

“…Indeed, the macroscopic deformation response of the natural tissue is dictated by the biphasic nature of the material, and the exceptional lubrication can be ascribed to the flow‐dependent (weeping) and flow‐independent (due to the solid matrix) viscoelasticity of its constituent, [ 16 ] coupled with the exceptional boundary lubricating properties of lubricin. [ 17 ] In our material, for the first time, the hydrogel substrate provides the loading support, while the top layer provides the brush‐ and weeping‐lubrication mechanisms. The latter, however, needs to be accurately designed as it might also unnecessarily increase the viscoelastic dissipation, thus the perceived friction, in the system.…”