Ординатура / Офтальмология / Английские материалы / Biomaterials and regenerative medicine in ophthalmology_Chirila_2010

on the soft contact lens surface. Reduced susceptibility of the phospholipid polymer to biofilm formation is noteworthy. Indeed, removal of bacterial biofilm is difficult using drug therapy and existing lens-disinfectant systems because of antibiotic-resistant bacteria. The advantages of the introduction of the phosphorylcholine headgroup into the material by chemical methods may translate into more effective disinfection, leading to reduced risk of contact lens-related eye infections for patients who use extended-wear soft contact lenses. Furthermore, omafilcon A is as good at relieving dry eye symptoms as soft contacts lenses with higher water contents such as hioxifilcon

G72-HW, which has a water content of 72% due to the advanced water wettability of the lenses induced by the MPC moiety (Riley et al., 2005). This water-retentive effect of the phospholipid polymer is quite important because dryness symptoms, especially reports of increasing dryness late in the day, have been cited in a number of studies as a reason for discontinuing or limiting lens wear.

10.5Phospholipid polymer for daily-disposable soft contact lenses

Daily-disposable lenses do not need lens treatment after removal from the eyes and thus there is less risk of infectious diseases. The simplicity in handling procedures and reasonable price have brought great commercial success for daily-disposable lens manufacturers in recent years. However, a significant number of people suffer from dry eye symptoms due to tear film break-up on the surface of the soft contact lenses. One strategy to improve wear comfort in a cost-effective way is the deposition or immobilization of hydrophilic polymers as wetting agents on daily-disposable soft contact lenses. For example, Johnson & Johnson brought out Acuvue® Moist™ for such a purpose. Although the bulk properties of the lenses remain the same as those of previous lenses manufactured from etafilcon A, the new lenses are formulated with a hydrophilic polymer, poly(NVP), which is immobilized in the matrix of etafilcon A to form an interpenetrating polymer network

(IPN) or semi-IPN structures, and is not released from the lens during wear. The coverage of the lens surface with the hydrophilic polymer in turn shows a 55% reduction in friction relative to the unmodified material when taken straight from the packaging solution (Ross et al., 2007). This should lead to an improvement in the overall comfort of the lenses. CIBA developed the Focus Dailies™ contact lens, which is made of nelfilcon A with the deposition of poly(vinyl alcohol) (PVA) by soaking in a PVA solution (Peterson et al., 2006). In this case, the hydrophilic polymer is released from the lenses during wear and thus produces a 25% reduction in friction on the lens surface compared with the original lenses. Similarly, CooperVision produced the One Day Aquair Evolution™ contact lens for the Japanese

Phospholipid BMA polymer

MPC

Deposition

(

( (

(

O

O

O

O

Vogt, 2001). Now, silicone hydrogel soft contact lenses are increasing in popularity with practitioners and patients for use as extended-daily-wear or continuous-wear lenses. The silicone polymers are well known for their high oxygen permeability compared with conventional polymers. The bulkiness of the siloxane group and high polymer chain mobility induce the high oxygen permeability of these materials. The silicone hydrogels are made of high oxygen permeable poly(dimethyl siloxane) (PDMS)-based macromers combined with various hydrophilic monomers to improve the rubbery characteristic and to increase the surface hydrophilicity of silicone. Additionally, silicone hydrogel materials can permeate some electrolytes dissolved in the tear fluid through the water phase in the hydrogel. Phase separation of silicone components and hydrophilic polymers in their bulk composition balances both the oxygen and electrolyte permeations (Tighe, 2004). Various approaches have been adopted by several manufacturers to produce silicone hydrogels with good mechanical properties, varied water content, and oxygen permeabilities. However, the problem with soft contact lens application is that the siloxane component tends to concentrate on the surface of the hydrogel, which creates a hydrophobic and biofouling surface. It has been found that the low surface energy of the native silicone hydrogels is vulnerable to adherent bacteria and cells. In other cases, the residual silicone oil from the retinal detachment treatment can also increase the incidence of endophthalmitis. Studies have shown that hydrophobic surfaces probably facilitate bacterial colonization and biofilm production, while hydrophilic surfaces seemed to be useful in limiting bacterial adherence and colonization (Kunz et al., 1999). Hence, the surface modification of silicone hydrogels is a promising approach for decreasing the incidence of endophthalmitis and improving biocompatibility. Surface modification techniques such as gas plasma treatment and graft polymerization of hydrophilic monomers on the lens surface have also been applied (Tighe, 2004). Both PureVision™

(balafilcon A, Bausch & Lomb) and Focus Night & Day™ (lotrafilcon A,

CIBA Vision) are treated using gas plasma techniques. The difference between these two products is that Bausch & Lomb have opted for plasma oxidation, whereas CIBA Vision has chosen to apply a plasma coating. In the former case, glassy islands are produced on the surface and in the latter case the coating is produced by a 25-nm-thick, dense, high-refractive-index coating. The dynamic contact angle results indicate that the two types of lenses have a very similar receding contact angle (qR) but different advancing contact angles (qA). Focus Night & Day™ lenses are appreciably more wettable than

PureVision™ lenses; the former lenses have a qA of 80° with a relatively low level of hysteresis of 35° and no significant change after 10 days of spoliation. PureVision™ lenses have a higher qA of 103° and a high level of hysteresis of 65°, with a slight increase in these values after 10 days of in vitro spoliation. One of the advantages of these plasma-treated methods

Poly(MPC) graft

Covalent bonding with silicone

contact angle decreased from 108º to 36º after the treatment. The reduction in the amount of bacterial adhesion on the treated surface was 60%. The results suggest that silicone hydrogel treated with MPC by the air plasma technique may be useful for contact lens applications.

10.7New developments

In designing a polymer hydrogel for advanced soft contact lens material with suitable bulk properties and biocompatibility, we should consider strategies not only to acquire sufficient oxygen transport and electrolyte permeability, render good mechanical properties, and form a homogeneous network structure as an optical material, but also to endow water wettability, protein adsorption resistance, and overall biocompatibility from the viewpoint of polymer chemistry and materials science. One known way to design soft contact lenses for extended and continuous wear is to add silicone-containing monomers to the hydrogel syntheses. Bulk phase morphology between the polysiloxane and a hydrophilic polymer is the crucial factor for determining oxygen permeability. A model analysis evaluation of phase-separated systems can predict that a complete phase separation (least amount of interphase regions) is essential for obtaining the high oxygen permeability that is theoretically achievable. In other words, a hydrogel forming a well-dispersed or miscible phase of polysiloxane exhibits low oxygen permeability, being far below the theoretical maximum value of a perfectly phase-separated silicone hydrogel (Nicolson and Vogt, 2001). Therefore, the main issue is how to organize a hybrid material made of silicone hydrogel and a hydrophilic polymer. Previous approaches to obtain hydrogels with high oxygen permeability were mainly based on the synthesis of biphasic materials, essentially represented by block-copolymers including polysiloxane and a hydrophilic polymer. However, the existing process for producing these biphasic materials is quite expensive and complicated in view of the necessity of performing a surface plasma treatment at the last stage of manufacturing. As an alternative method for bulk modification, a biphasic silicone preparation based on

IPN formation has recently been developed for ophthalmologic materials (Chekina et al., 2006). The physical entanglements of the polymer chains improve both the bulk and surface stability of the material. The IPN structure is able to combine different polymer properties, while at the same time minimizing any incompatibility effects. Therefore, this approach avoids the need to synthesize new compounds or to make surface treatments. In 2004, intrinsically wettable silicone hydrogel lens materials such as Acuvue® Advance® (galyfilcon A, Johnson & Johnson) and Acuvue® Oasys® (senofilcon

A, Johnson & Johnson) were released. These lenses incorporate poly(NVP) as a wetting agent via IPN and thus require no surface treatment. They show higher oxygen permeability with higher water content than previous

prepared by the following three steps. (a) A cross-linked poly(SiGMA) hydrogel is synthesized by UV irradiation with a cross-linker and photosensitizer. (b)

The purified poly(SiGMA) hydrogel is then immersed in a solution of MPC in isopropanol to become fully swollen. (c) The cross-linked poly(MPC) network is then formed in the silicone hydrogel by the same method as the formation of the first network. The obtained hybrid material with a water content of 41% shows extreme hydrophilicity, and its superior protein adsorption resistance originates in the second poly(MPC) network on the surface, together with optical transparency, flexibility, and oxygen permeability (111 barrer) derived from the first poly(SiGMA) network. Notably, the water contact angle on the

IPN hydrogel surface is measured to be 0º by the captive bubble technique. Surface analysis indicates that such an extremely hydrophilic surface of the IPN hydrogel is achieved by the enrichment of the MPC unit on the outermost surface. The amount of protein adsorption on the IPN hydrogel is 28% of that on the poly(SiGMA) hydrogel. The IPN hydrogel may be a strong candidate for use with continuous-wear soft contact lens materials, showing advanced wear comfort and biocompatibility.

10.8Conclusions

In this chapter we described the application of a bioinspired phospholipid polymer for enhancement of the biocompatibility of daily, daily-disposable, extended-wear or continuous-wear soft contact lenses in various ways. As a result of the development of MPC as a main constituent showing biocompatibility in the artificially synthesized phospholipid polymer, various chemical methods can be used to introduce a bioinspired phospholipid polymer into a wide variety of soft contact lens materials. The phospholipid polymer not only reduces the frequency of eye dryness symptoms because of its hydrophilic and water-retentive nature, but also reduces susceptibility to biofilm formation followed by non-specific protein adsorption prevention.

These properties of the phospholipid polymer favorably decrease the potential risk of endophthalmitis related to contact lens wear.

10.9Future trends

Advances in materials suitable for the high-volume, low-cost production necessary for today’s daily-disposable lenses market will continue. By replacing soft contact lenses more often, patients can avoid potential risks associated with deposits, including reduced visual acuity, lens comfort, and wettability. Most companies are now introducing the next generation of dailydisposable lenses that are expected to offer better comfort and vision than their predecessors. Many more lenses are also now starting to be marketed specifically to help wearers who suffer from dryness symptoms. In the past,

276 Biomaterials and regenerative medicine in ophthalmology

the lenses available had in a restricted range of properties, which limited the type and number of patients who might benefit. Thanks to the development of new lens materials, a wide variety of patients with dryness symptoms can now wear the new, more comfortable lenses.

Macroscopically, the market will polarize into continuous wear and daily-disposable wear, driven by wearers seeking better oxygen supply, biocompatibility, and wear comfort at reasonable prices. At the same time, the development of diverse soft contact lenses will result in unlimited numbers and types of patients who might benefit, by providing such patients with the most suitable lenses. The use of a phospholipid polymer for soft contact lenses in an effective way will help the material to elevate overall biocompatibility.

10.10 Sources of further information and advice

The MPC as a base component of phospholipid polymers is now prepared on an industrial scale by NOF Co. (Tokyo, Japan) based on our results (Ishihara et al., 1990a). The fundamental biological data of phospholipid polymers have been reported in the literature (Ishihara et al., 1990b, 1991,

1992; Defife et al., 1995; Ueda et al., 1995; Sakaki et al., 1999; Sawada et al., 2003, 2006). The phospholipid polymer is developed not only for soft contact lenses, but also for other biomedical applications. For example, one of the most successful applications is in artificial joints (Moro et al., 2004). Nanoscaled grafting of the poly(MPC) on to the cross-linked polyethylene surface provides good lubricity, wear resistance, and biocompatibility in biological environments (Kyomoto et al., 2007). Such excellent functions of the modified surface could avoid the activation of cell systems by the wear particles, thus entirely preventing periprosthetic osteolysis and subsequent aseptic loosening. In addition, prevention of non-specific protein adsorption is very useful for the reduction of noise intensity in biosensors and for enhancing affinity in enzyme-linked immuno-sorbent assays (Goto et al., 2008).

10.11 References

Chekina N, Pavlyuchenko V, Danilichev V, Ushakov N, Novikov S and Ivanchev S (2006), ‘A new polymeric silicone hydrogel for medical applications: synthesis and properties’, Polym Adv Technol, 17, 872–877. DOI: 10.1002/pat.820.

Chen C, Hong Y and Manesis N (2008), ‘Wettable silicone hydrogel contact lenses and related compositions and methods’, US Patent Application 20080048350.

Colman R and Schmaier A (1997), ‘Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes’, Blood,

90, 3819–3843.

Dang Y, Rao A, Kastl P, Blake R, Schurr M and Blake D (2003), ‘Quantifying Pseudomonas aeruginosa adhesion to contact lenses’, Eye Contact Lens, 29, 65–68.

Defife K, Yun J, Azeez A, Stack S, Ishihara K, Nakabayashi N, Colton E and Anderson J (1995), ‘Adhesion and cytokine production by monocytes on poly(2- methacryloyloxyethyl phosphorylcholine-co-alkyl methacrylate)-coated polymers’, J Biomed Mater Res, 29, 431–439. DOI: 10.1002/jbm.820290403.

Goda T, Konno T, Takai M, Moro T and Ishihara K (2006), ‘Biomimetic phosphorylcholine polymer grafting from polydimethylsiloxane surface using photo-induced polymerization’, Biomaterials, 27, 5151–5160. DOI: 10.1016/j.biomaterials.2006.05.046.

Goto Y, Matsuno R, Konno T, Takai M and Ishihara K (2008), ‘Polymer nanoparticles covered with phosphorylcholine groups and immobilized with antibody for high- affinity separation of proteins’, Biomacromolecules, 9, 828–833. DOI: 10.1021/ bm701161d.

Harvitt D and Bonanno J (1999), ‘Re-evaluation of the oxygen diffusion model for predicting minimum contact lens Dk/t values needed to avoid corneal anoxia’, Optom Vis Sci, 76, 712–719.

Ho S, Nakabayashi N, Iwasaki Y, Boland T and LaBerge M (2003), ‘Frictional properties of poly(MPC-co-BMA) phospholipid polymer for catheter applications’, Biomaterials, 24, 5121–5129. DOI: 10.1016/S0142-9612(03)00450-2.

Huang X, Yao K, Zhang H, Huang H and Xu Z (2007), ‘Surface modification of silicone intraocular lens by 2-methacryloyloxyethyl phosphoryl-choline binding to reduce

Staphylococcus epidermidis adherence’, Clin Exper Ophthalmol, 35, 462–467. DOI: 10.1111/j.1442-9071.2007.01516.x.

Ishihara K, Ueda T and Nakabayashi N (1990a), ‘Preparation of phospholipid polylners and their properties as polymer hydrogel membranes’, Polym J, 22, 355–360.

Ishihara K, Aragaki R, Ueda T, Watanabe A and Nakabayashi N (1990b), ‘Reduced thrombogenicity of polymers having phospholipid polar groups’, J Biomed Mater Res, 24, 1069–1077. DOI: 10.1002/jbm.820240809.

Ishihara K, Ziats N, Tierney B, Nakabayashi N and Anderson J (1991), ‘Protein adsorption from human plasma is reduced on phospholipid polymers’, J Biomed Mater Res, 25, 1397–1407. DOI: 10.1002/jbm.820251107.

Ishihara K, Oshida H, Endo Y, Ueda T, Watanabe A and Nakabayashi N (1992), ‘Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism’, J Biomed Mater Res, 26, 1543–1552. DOI: 10.1002/ jbm.820261202.

Ishihara K, Nomura H, Mihara T, Kurita K, Iwasaki Y and Nakabayashi N (1998), ‘Why do phospholipid polymers reduce protein adsorption?’, J Biomed Mater Res, 39, 323–330.

DOI: 10.1002/(SICI)1097-4636(199802)39:2<323::AID-JBM21>3.0.CO;2-C.

Iwasaki Y and Ishihara K (2005), ‘Phosphorylcholine-containing polymers for biomedical applications’, Anal Bioanal Chem, 381, 534–546. DOI: 10.1007/s00216-004- 2805-9.

Jones L, Evans K, Sariri R, Franklin V and Tighe B (1997), ‘Lipid and protein deposition of N-vinyl pyrrolidone-containing group II and group IV frequent replacement contact lenses’, CLAO J, 23, 122–126.

Keith D, Christensen M, Barry J and Stein J (2003), ‘Determination of the lysozyme deposit curve in soft contact lenses’, Eye Contact Lens, 29, 79–82.

Kitano H, Imai M, Mori T, Gemmei-Ide M, Yokoyama Y and Ishihara K (2003), ‘Structure of water in the vicinity of phospholipid analogue copolymers as studied by vibrational spectroscopy’, Langmuir, 19, 10260–10266. DOI: 10.1021/la0349673.

Kunz R, Anders C, Heinrich L and Gersonde K (1999), ‘Investigation into the mechanism of bacterial adhesion to hydrogel-coated surfaces’, J Mater Sci Mater Med, 10, 649–652. DOI: 10.1023/A:1008943909728.

278 Biomaterials and regenerative medicine in ophthalmology

Kyomoto M, Moro T, Konno T, Takadama H, Yamawaki N, Kawaguchi H, Takatori Y,

Nakamura K and Ishihara K (2007), ‘Enhanced wear resistance of modified cross- linked polyethylene by grafting with poly(2-methacryloyloxyethyl phosphorylcholine)’, J Biomed Mater Res A, 82, 10–17. DOI: 10.1002/jbm.a.31134.

Ladage P, Yamamoto N, Robertson D, Jester J, Petroll W and Cavanagh H (2004), ‘Pseudomonas aeruginosa corneal binding after 24-hour orthokeratology lens wear’,

Eye Contact Lens, 30, 173–178.

Matsuda Y, Kobayashi M, Annaka M, Ishihara K and Takahara, A (2006), ‘Dimension of poly(2-methacryloyloxyethyl phosphorylcholine) in aqueous solutions with various ionic strength’, Chem Lett, 35, 1310–1311. DOI: 10.1246/cl.2006.1310.

Moro T, Takatori Y, Ishihara K, Konno T, Takigawa Y, Matsushita T, Chung U-I,

Nakamura K and Kawaguchi H (2004), ‘Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis’, Nat Mater, 3, 829–836. DOI: 10.1038/nmat1233.

Nicolson P and Vogt J (2001), ‘Soft contact lens polymers: an evolution’, Biomaterials, 22, 3273–3283. DOI: 10.1016/S0142-9612(01)00165-X.

Peterson R, Wolffsohn J, Nick J, Winterton L and Lally J (2006), ‘Clinical performance of daily disposable soft contact lenses using sustained release technology’, Cont Lens Anterior Eye, 29, 127–134. DOI: 10.1016/j.clae.2006.03.004.

Ratner B D, Hoffman A S, Schoen F J and Lemons J E eds (2004), Biomaterials Science, 2nd edn, Amsterdam, Elsevier.

Riley C, Chalmers R and Pence N (2005), ‘The impact of lens choice in the relief of contact lens related symptoms and ocular surface findings’, Cont Lens Anterior Eye,

28, 13–19. DOI: 10.1016/j.clae.2004.09.002.

Ross G, Mann A, Franklin V and Tighe B (2007), ‘Disclosure – the true story of daily disposable lens surfaces’, In 31st BCLA Clinical Conference and Exhibition, 31 May-3 June, Manchester, UK, p. 122.

Sakaki S, Nakabayashi N and Ishihara K (1999), ‘Stabilization of an antibody conjugated with enzyme by 2-methacryloyloxyethyl phosphorylcholine copolymer in enzymelinked immunosorbent assay’, J Biomed Mater Res A, 47, 523–528. DOI: 10.1002/

(SICI)1097-4636(19991215)47:4<523::AID-JBM8>3.0.CO;2-J.

Sawada S, Sakaki S, Iwasaki Y, Nakabayashi N and Ishihara K (2003), ‘Suppression of the inflammatory response from adherent cells on phospholipid polymers’, J Biomed Mater Res A, 64, 411–416. DOI: 10.1002/jbm.a.10433.

Sawada S, Iwasaki Y, Nakabayashi N and Ishihara K (2006), ‘Stress response of adherent cells on a polymer blend surface composed of a segmented polyurethane and MPC copolymers’, J Biomed Mater Res A, 79, 476–484. DOI: 10.1002/jbm.a.30820.

Selan L, Palma S, Scoarughi G, Papa R, Veeh R, Clemente D and Artini M (2009),

‘Phosphorylcholine impairs susceptibility to biofilm formation of hydrogel contact lenses’, Am J Ophthalmol, 147, 134–139. DOI: 10.1016/j.ajo.2008.07.032.

Shaku M, Kuroda H, Oba A, Okura S, Ishihara K and Nakabayashi N (1997), ‘Enhancing stratum corneum functions with a bifunctional phospholipid polymer’, Cosmet Toiletries, 112, 65–76.

Shimizu T, Goda T, Konno T, Takai M and Ishihara K (2008), ‘Improved protein adsorption on soft contact lenses treated with phospholipid polymers’, In 8th World Biomaterials Congress, 28 May–1 June 2008, Amsterdam, The Netherlands, abstract P-Sat-I-565, p. 2249.

Shimizu T, Konno T, Takai M and Ishihara K (2009), ‘Super hydrophilic surface realized by IPN structure of silicone hydrogel’, In Proceedings of IUMRS-ICA, Symposium K, 9–13 December 2008, Nagoya, Japan, KO-10 (in Press).