Hydration Lubrication in Biomedical Applications: From Cartilage to Hydrogels

Abstract

In the course of evolution, nature has achieved remarkably lubricated surfaces, with healthy articular cartilage in the major (synovial) joints being the prime example, that can last a lifetime as they slide past each other with ultralow friction (friction coefficient μ = the force to slide surfaces past each other/load compressing the surfaces < 0.01) under physiological pressures (up to 10 MPa or more)). Such properties are unmatched by any man-made materials. The precise mechanism of low friction between such sliding cartilage tissues, which is closely related to osteoarthritis (OA), the most widespread joint disease, affecting hundreds of millions worldwide, has been studied for nearly a century, but is still not fully understood. Traditionally, the roles of load bearing by interstitial fluid within the cartilage bulk and that of thin exuded fluid films at the interface between the sliding cartilage surfaces have been proposed as the main lubrication mechanism. More recent work, however, suggests that molecular boundary layers at the surfaces of articular cartilage and other tissues play a major role in their lubrication. In particular, in recent years hydration lubrication has emerged as a new paradigm for boundary lubrication in aqueous media based on subnanometer hydration shells which massively reduce frictional dissipation. The vectors of hydration lubrication include trapped hydrated ions, hydrated surfactants, biological macromolecules, biomimetic polymers, polyelectrolytes and polyzwitterionic brushes, and close-packed layers of phosphatidylcholine (PC) vesicles, all having in common the exposure of highly hydrated groups at the slip plane. Among them, vesicles (or bilayers) of PC lipids, which are the most widespread lipid class in mammals, are exceptionally efficient lubricating elements as a result of the high hydration of the phosphocholine headgroups they expose. Such lipids are ubiquitous in joints, leading to the proposal that macromolecular surface complexes exposing PC bilayers are responsible for the remarkable lubrication of cartilage. Cartilage, comprising ∼70% water, may be considered to be a complex biological hydrogel, and studying the frictional properties of hydrogels may thus provide new insights into its lubrication mechanisms, leading in turn to novel, highly lubricious hydrogels that may be used in a variety of biomedical and other applications. A better understanding of cartilage lubrication could moreover lead to better treatments for OA, for example, through intra-articular injections of appropriate lubricants or through the creation of low-friction hydrogels that may be used as tissue engineering scaffolds for diseased cartilage. In this Account, we begin by introducing the concept and origin of hydration lubrication, extending from the seminal study of lubrication by hydrated simple ions to more complex systems. We then briefly review different modes of lubrication in synovial joints, focusing primarily on boundary lubrication. We consider modes of hydrogel lubrication and different kinds of such low-friction synthetic gels and then focus on cartilage-inspired, boundary-lubricated hydrogels. We conclude by discussing challenges and opportunities.

Figure 1

(a) Illustrating the large dipole moment of a water molecule due to the difference in the electronegativity of atoms (top left), a hydration shell of water molecules surrounding a positively charged ion (top right), and the hydration repulsion of steric origin due to the overlapped hydration layer of two similar charges (bottom). (b) Hydrated Na⁺ ions trapped between two negatively charged mica surfaces which are ca. 1 nm apart, where the spacing of the mica surface lattice sites is ca. 0.7 nm. This hydration layer can bear a large load without being squeezed out, while the molecular exchange rate between the water molecules in the hydration layer and bulk water, or other hydration layers, is very fast and ensures its fluidity.^, (c) Schematic illustration of a surface forces balance (SFB) for directly measuring normal and shear forces between two molecularly smooth, back-silvered mica surfaces. The absolute separation D (to ±2 Å) between two mica surfaces can be evaluated from multiple-beam interference, enabling normal forces to be measured by the bending of the horizontal leaf spring S₂. Shear forces are determined via an air-gap capacitance probe, which measures the bending of the vertical leaf springs S₁. (d) Normal force profiles between two mica surfaces across 0.007 ± 0.002 M (empty symbols) and 0.08 ± 0.01 M (solid symbols) of NaCl solution. Strong hydration repulsion due to an overlap of hydration shells on the trapped counterions was seen for D < ca. 2 nm during compression. (a) Reproduced with permission from ref (6). Copyright 2013 Springer-Verlag. (b and d) Reproduced with permission from ref (7). Copyright 2002 AAAS. (c) Reproduced with permission from ref (9). Copyright 2021 Wiley-VCH.

Figure 2

(a) PMPC polymer brush grafted directly from a mica surface can have a CoF of as low as 10^–4 at pressures as high as 150 atm or more because of the intensive hydration of the strongly attached brushes consisting of phosphorylcholine-like monomers.^, (b) Hydrogenated soybean phosphatidylcholine (HSPC) liposomes are closely packed on a mica surface in the form of intact vesicles, which reduce the CoF down to μ ≈ 10^–4–2 × 10^–5 under a pressure of up to ca. 120 atm. This ultralow friction under physiologically high pressures is attributed to lubrication by the highly hydrated phosphocholine headgroups exposed at the interfaces, with close-packing structures on the sliding substrates and strong interactions between hydrophobic tails. (c) Swelling δD is observed when surfactant-monolayer-coated mica surfaces in air (layer thickness of D₀) are immersed in water (layer thickness of D₀ + δD), attributed to the hydration of the surface-attached headgroups. This hydration layer leads to a reduction in sliding friction via the hydration lubrication mechanism so that during surface shear under water the slip plane reverts from hydrophobic tails to the headgroup/mica interface. (d) Homo-oligomeric phosphocholinated micelles demonstrate excellent lubrication and are much more robust than single-tail phosphocholinated surfactants as a result of the greater energy required to remove a homo-oligomeric molecule from its micelle structure. The strong reduction in sliding friction can be attributed to hydration lubrication by the highly hydrated phosphocholine groups of the oligomer that are exposed at the interface between the close-packed micelles on the sliding substrates. (e) Schematic of the amphiphilic protein hydrophobin (HFBI) structure. The friction between HFBI proteins adsorbed hydrophobic-side down on hydrophobized mica (exposing their hydrated hydrophilic surfaces) is much lower than the friction between HFBI-coated hydrophilic surfaces (exposing the hydrophobic patches of the HFBI at the slip plane). (f) Schematic of the bottle-brush polymer inspired from the structure of lubricin. The lubricin-mimicking polymer consists of two cationic adhesive domains at its ends, and a central bottle-brush domain containing a flexible backbone modified with highly hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brushes. CoF is as low as ∼10^–3 under physiological pressures as a result of the exposure of the highly hydrated grafted PMPC brushes. (a) Reproduced with permission from ref (11). Copyright 2009 AAAS. (b) Reproduced with permission from ref (12). Copyright 2011 Wiley-VCH. (c) Reproduced with permission from ref (13). Copyright 2006 Nature Publishing Group. (d) Reproduced with permission from ref (14). Copyright 2020 American Chemical Society. (f) Reproduced with permission from ref (15). Copyright 2013 Royal Society of Chemistry. (e) Reproduced with permission from ref (16). Copyright 2014 American Chemical Society.

Figure 3

(a) Illustration of a synovial joint and its boundary layer consisting of linear hyaluronic acid (HA, gray), mucinous glycoprotein lubricin (purple), and phospholipids (monolayer, green; bilayer, blue) on a collagen network (orange). (b) In a fluid-film lubrication mode, a thin liquid layer separates the cartilage surfaces as they slide, with few asperity contacts, reducing the friction and wear markedly, and the shear stress σ_s may be written in the Newtonian form, σ_s = (shear rate) × (effective fluid viscosity). (c) In the boundary lubrication mode, frictional dissipation occurs at the interface between the opposing, contacting boundary layers and depends strongly on the detailed molecular structure at that interface, but it is largely independent of the substrates beneath the boundary layers. (a) Reproduced with permission from ref (27). Copyright 2016 Annual Review. (b and c) Reproduced with permission from ref (9). Copyright 2021 Wiley-VCH.

Figure 4

(a) Illustration of liposomes adsorbed on an HA-bearing surface, and the boundary layer structure proposed following compression and shear. (b) SEM image of HSPC liposomes attached on an HA-bearing mica surface. (c) Shear force F_s versus normal force F_n profiles between mica surfaces bearing surface layers of lipids complexed with HA, across purified water (black symbols) and across 150 mM KNO₃ (red symbols). (a and b) Reproduced with permission from ref (36). Copyright 2017 Elsevier. (c) Reproduced with permission from ref (37). Copyright 2015 Nature Publishing Group.

Figure 5

Illustration of the difference between lubrication by PMPC brushes grown from a mica surface ((a) left-hand cartoon) and the same brushes once they are internally cross-linked to form a thin gel-like layer ((a) right-hand cartoon). In both cases, the friction F_s is low, mediated by the hydration lubrication mechanism at the highly hydrated phosphocholine groups, but the dependence on sliding velocity v_s is very different ((a) center panel, μ ≈ 10^–4 for brushes and μ ≈ 10^–3–10^–4 depending on the v_s for cross-linked brushes). (a) Comparison of the friction F_s versus sliding velocity v_s between PMPC brushes (black symbols) and PMPC hydrogel-like layers (purple symbols). (b) Schematic illustrations of the interpenetration zone (shaded area) between two compressed layers of either linear brushes or hydrogel-like cross-linked brushes. In the former case, the thinner interpenetration region at higher sliding velocities offsets the higher energy dissipation at such velocities, leading to very weakly velocity-dependent shear force (black data points in (a)). Reproduced with permission from ref (21). Copyright 2017 American Chemical Society.

Figure 6

(a) CoF values of different hydrogels (DN, TN, and DN-L) against a glass plate in pure water. (b) A polymer-filled microporous hydrogel reduces friction when sliding against a rigid counter face under normal and shear forces. (c) Schematic illustration of the fabrication procedures of cartilage-mimicking PSPMA or PSBMA brush-grafted hydrogels. (a) Reproduced with permission from ref (51). Copyright 2011 Wiley-VCH. (b) Reproduced with permission from ref (57). Copyright 2020, Elsevier. (c) Reproduced with permission from ref (58). Copyright 2020 Wiley-VCH.

Figure 7

(a) Schematic diagram of a self-lubricating hydrogel containing phospholipids. (b) Freeze-fracture surface of the hydrogel containing DMPC vesicles by cryo-SEM, showing the microreservoirs transected by the surface. (c) Single microreservoir from (b) at higher magnification. (d) CoF of the hydrogel under different pressures. (e) CoF values of the lipid-free and HSPC-incorporating hydrogels under different pressures after rehydration, maintaining the characteristic self-lubricating ability for the latter. (f) Comparison of wear conditions of lipid-free and DMPC-incorporating gels. Reproduced with permission from ref (60). Copyright AAAS.