Langmuir.2016 Oct;32(42):10957-10966

Insight into the Tribological Behavior of Liposomes in Artificial Joints

Yiqin Duan1, Yuhong Liu1,*, Caixia Zhang2, Zhe Chen1, Shizhu Wen1

1State Key Laboratory of Tribology, Tsinghua University, Beijing 100084, China

2 Beijing Key Laboratory of Advanced Manufacturing Technology, Beijing University of Technology, Beijing 100124, China

Correspondence should be addressed to Yuhong Liu, E-mail: liuyuhong@tsinghua.edu.cn

 

Abstract

Liposomes are widely used in drug delivery and gene therapy, and their new role as boundary lubricant in natural/artificial joints has been found in recent years. In this study, the tribological properties of liposomes on titanium alloy (Ti6Al4V)/UHMWPE interface were studied by a ball-on-disc tribometer. The efficient reduction of friction coefficient and wear on both surfaces under various velocities and loads is found. A multilayer structure of physically adsorbed liposomes on Ti6Al4V surface was also observed by atomic force microscope (AFM). Except for the hydration mechanism by phosphatidylcholine (PC) groups, the well-performed tribological properties by liposomes is also attributed to the existence of adsorbed liposomes layers on both surfaces, which could reduce asperities contact and show great bearing capacity. This work enriches the research on liposomes for lubrication improvement on artificial surface and shows their value on clinical application.

 

Supplement

The adsorption morphology of DPPC on Ti6Al4V was obtained by AFM, shown in Figure 1. When lipid concentration is 1mg/ml (Figure 1(a)), the coating is composed of a close-packed layer of liposomes, with a loose coating of aggregated liposomes on top of this layer. When scanning the same area by AFM tip for several times, the close-packed liposomes in lower layer appear (inset). The height of this flattened liposome is 50±10 nm, which is much lower than the unperturbed liposome height from DLS result (122±35 nm), due to attraction force from substrate and compression by AFM tip. By decreasing the lipid concentration (Figure 1(b-d)), there are fewer and flatter liposomes on top layer (mark a). Meanwhile, in lower layer (insets), due to the stronger attraction force from substrate, large liposomes rupture to bilayers1 with thickness of 5 nm and smaller liposomes are flattened with height of 10 nm, which is equal to a double value of one bilayer (mark b).

Based on the AFM results, the sequential adsorption process and mechanisms of liposome vesicles are proposed in Figure 1(e-g). For a single vesicle (Figure 1(e)), the closed structure (from strong chain-chain hydrophobic attractions2) and the lateral constraints arising from neighboring vesicles could keep vesicles intact and robust. However, the forces arising from the substrate, AFM tip1 tend to rupture the bilayer membrane. Thus, adsorbed liposomes are metastable, especially for these liposomes which are firstly adsorbed on Ti6Al4V substrate (They rupture to bilayers with thickness of 5-6 nm). For subsequent liposomes, they would retain their closed shape, due to decreased attraction forces (Figure 1(f)). As a result, a multilayer structure of liposomes adsorbed on Ti6Al4V substrate is proposed as Figure 1(g).

 

 

Figure 1. AFM images of liposomes absorbed onto Ti6Al4V with lipid concentrations of (a) 1 mg/ml, (b) 0.1 mg/ml, (c) 0.05 mg/ml, and (d) 0.01 mg/ml. Insets in the bottom left corner are images below top layers. (e) Mechanical analysis of liposome vesicles. (f) – (g) Schemes of continuous adsorption process of vesicles and final structure of liposomes adsorbed on Ti6Al4V substrate. Scale bars are 500 nm.

 

The adsorption morphology of DPPC on UHMWPE was obtained by AFM, shown in Figure 2. Similarly, with lipid concentration of 1mg/ml, there is a dense distribution of liposomes on UHMWPE3. So far, the liposomes are found on both sliding surfaces with a high lipid concentration. Notably, there is a difference on the adsorption strength between liposomes and two surfaces. Compared with Figure 2(b) and Figure 1(d), it is obvious that liposomes cannot stay on UHMWPE surface with low lipid concentration, since UHMWPE is known as a hydrophobic polymer4.

 

 

Figure 2. AFM images of liposomes absorbed onto UHMWPE foil with lipid concentrations of (a) 1 mg/ml and (b) 0.01 mg/ml. Insets in the bottom left corner are images below top layers. Scale bars are 500 nm.

 

To study the tribological behaviors of DPPC liposomes on Ti6Al4V against UHMWPE, four friction tests were conducted using ball-on-disc equipment. It is worth noting that the velocity and normal load are related to the friction coefficient according to Stribeck Curve5. From Figure 3(a), there is an excellent friction reduction by DPPC liposomes under all velocities. Besides, the average friction coefficient by DPPC is stable mostly due to the same wear scars on UHMWPE surfaces under different velocities. To the contrary, the wear scar is severer under higher velocity when lubricated by water, causing high friction. Meanwhile, there is also an obvious friction reduction by DPPC liposomes under all loads from Figure 3(b). Even under high load of 400g (ca.39MPa), the friction is low in the case of DPPC, which means that the adsorbed layer on both surface can prevent asperities contact.

Since the vesicle size and lipid concentration can directly influence the structure of boundary layers, it is considerable in our study. Figure 3(c) gives a clear sight that the lowest friction coefficient is achieved under size around 100 nm. Because the vesicles are well-distributed on adsorbed layer with uniform size, the energy dissipation is low when two surfaces sliding past each other. As for the impact of lipid concentration, the decrease in average friction coefficient indicates higher lipid concentration could form a thicker adsorbed layers, leading to better bearing capacity, shown in Figure 3(d).

 

 

Figure 3. (a) Effect of sliding velocity on average friction coefficient. The lipid concentration is 1mg/ml and normal load is 2N (P=ca. 30.87 MPa). (b) Effect of normal load on average friction coefficient. The lipid concentration is 1mg/ml and sliding velocity is 0.3 mm/s. (c) Average friction coefficient with three membrane pore sizes and their mixture (lipid concentration is 1 mg/ml). (d) Effect of lipid concentration on average friction coefficient (vesicle size is around 100 nm). Experiments in Fig(c) and (d) were carried out under load of 2 N (P=ca. 30.87 MPa), sliding velocity of 0.3 mm/s.

 

At last, a lubrication model is proposed in Figure 4. The rubbing of two surfaces can be considered as the mechanical effect of asperities from surfaces. Between these asperities, a mount of liposomes exist and form the adsorbed layers. Liposomes physically adsorb onto two surfaces, with stronger attraction interaction towards Ti6Al4V surface due to hydrophilicity and opposite charges. A multilayer structure is formed and shear slip happen within these layers. The low friction is achieved by the highly hydrated PC groups6 exposed in water, where liposome vesicles move easily between each other. Meanwhile, adsorbed liposomes layers show great bearing capacity and wear resistance due to elastic property1 of vesicle and softness of adsorbed films, which contribute to the low friction.

 

 

Figure 4. Schematic illustration of the lubrication model by liposomes between Ti6Al4V- UHMWPE surfaces.

 

 

References

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(2) Sorkin, R.; Kampf, N.; Dror, Y.; Shimoni, E.; Klein, J. Origins of Extreme Boundary Lubrication by Phosphatidylcholine Liposomes. Biomaterials 2013, 34, 5465-5475.

(3) Bruck, A. L.; Kanaga Karuppiah, K. S.; Sundararajan, S.; Wang, J.; Lin, Z. Friction and Wear Behavior of Ultrahigh Molecular Weight Polyethylene as a Function of Crystallinity in the Presence of the Phospholipid Dipalmitoyl Phosphatidylcholine. J. Biomed. Mater. Res., Part B 2010, 93B, 351-358.

(4) Pawlak, Z.; Urbaniak, W.; Oloyede, A. The Relationship Between Friction and Wettability in Aqueous Environment. Wear 2011, 271, 1745-1749.

(5) Kalin, M.; Velkavrh, I.; Vizintin, J. The Stribeck Curve and Lubrication Design for Non-Fully Wetted Surfaces. Wear 2009, 267, 1232-1240.

(6) Klein, J. Hydration Lubrication. Friction 2013, 1, 1-23.