Hydrophobic modification of polymethyl methacrylate as intraocular lenses material to improve the cytocompatibility

https://doi.org/10.1016/j.jcis.2014.05.056Get rights and content

Highlights

Abstract

The development of posterior capsule opacification (PCO) after intraocular lenses (IOL) implantation for dealing with cataract is mainly due to the severe loss of the human lens epithelial cells (HLECs) during surgery contact. A novel poly (hedral oligomeric silsesquioxane-co-methyl methacrylate) copolymer (allyl POSS–PMMA) was synthesized by free radical polymerization method to promote the adhesion of HLECs. FT-IR and 1H NMR measurements indicated the existence of POSS cage in the product, which demonstrated the successful synthesis of allyl POSS–PMMA copolymer. Effect of allyl POSS in the hybrids on crystal structure, surface wettability and morphology, optical transmission, thermodynamic properties and cytocompatibility was investigated in detail. X-ray diffraction peaks at 2θ∼11° and 12° indicated that POSS molecules had aggregated and crystallized. Thermogravimetric analysis-differential scanning calorimeter and optical transmission measurements confirmed that the allyl POSS–PMMA copolymer had high glass transition temperatures (more than 100 °C) and good transparency. The hydrophilicity and morphology of PMMA and copolymers surfaces were characterized by static water contact angle and atomic force microscopy. The results revealed that the surface of the allyl POSS–PMMA copolymer displayed higher hydrophobicity and higher roughness than that of pure PMMA. The surface biocompatibility was evaluated by morphology and activity measurement with HLECs in vitro. The results verified that the surface of allyl POSS–PMMA copolymer films had more HLECs adhesion and better spreading morphology than that of PMMA film.

Introduction

Cataract surgery has increased rapidly in recent decades. Phacoemulsification combined with intraocular lenses (IOL) implantation is the first choice for cataract treatment on account of small incision, quick recovery and better postoperative vision [1], [2], [3]. However, posterior capsule opacification (PCO) is a common complication after cataract surgery caused by the immune response and residual human lens epithelial cells (HLECs) on the posterior capsule [4]. Wound healing promotes residual HLECs to proliferate, differentiate, and to deposit extracellular matrix, via autocrine and paracrine cell signaling. Although PCO has been extensively studied, there is no unified mechanism to explain the cause. Most current studies hypothesize that a multicellular secondary membrane results from migration and fibrosis of residual HLECs on the posterior capsule, forming elschnig pearls [5]. Others suggest that a single layer of residual anterior capsule epithelial cells migrate onto the posterior capsule and undergo metaplasia into myofibroblasts, pulling the posterior capsule into many tiny folds. Both mechanisms can contribute to the development of PCO [6].

In recent years, several reports have focused on how to prevent PCO. In addition to the position of the capsulorhexis, IOL material and optic design are important factors in the development of PCO [7], [8], [9]. The effect of IOL on PCO has been explained by various suppositions such as the separation of the posterior capsule from the anterior capsule, stretching of the capsule, compression, no space/no cells and adhesiveness of the IOL material. Out of all of the commercial IOLs, hydrophobic acrylic IOL especially poly (methyl methacrylate) (PMMA) has played an important role in cataract surgery soon after its introduction in the mid-1990s [10], [11]. PMMA is the most common commercially available IOL material and is known for long-term stability. It is relatively inexpensive, inert and is well tolerated in the eye with minimal inflammatory reaction. PMMA IOL has good light transmission properties which can transmit a broad spectrum of light including near-ultraviolet light [12]. Unfortunately, the surgery contact can cause considerable HLECs loss between the comparatively hard PMMA IOL surface and the corneal endothelium. Based on the sandwich theory [13], [14], [15] of PCO, the rapid epithelialization of IOL that forms a cell monolayer between IOL and posterior capsule can fill up the space and finally reduce the occurrence of PCO.

The surface properties of a polymer can be modified in order to ensure that it will be better adapted to its final use. Basically, the surface energy of the polymer (hydrophilic vs. hydrophobic nature) can be modified according to two general methods: surface treatment and bulk modification. The surface treatment methods of PMMA mainly include plasma treatment [16], nanoparticles doping [17] and grafting of biological macromolecules [18], [19], [20]. The plasma treatment used as a surface modification method is simple, effective and without safety issues. Using plasma discharge, hydroxyl, carboxyl or other hydrophilic functional groups can be introduced onto the surface of intraocular lenses to improve its biocompatibility. Titanium dioxide nanoparticles have been used to modify IOL to enhance its biocompatibility [17]. Heparin surface modification (HSM) decreases adhesion of cells and inflammations after cataract surgery [18]. However, a recent study shows the ratio of PCO is high using HSM IOL. Recently, a 2-methacryloyloxyethyl phosphorylchoine (MPC) coating was produced, which decreased adhesion of platelet, macrophage, lens epithelial cells and bacteria [19]. Although plasma treatment method can alter the surface wetting properties of IOL, the hydrophilic performance may lose in a short time. Metal oxide nanoparticles and biomolecules modified intraocular lenses always have color and unstable defects. Comparatively, bulk modification is a stable, effective and controllable IOL modified method.

Polyhedral oligomeric silsesquioxane (POSS) is a novel cage-like structure of the organic–inorganic hybrid molecules [21], [22], [23]. The main structure of POSS consists of two parts: a cage-like inorganic core based on Sisingle bondOsingle bondSi bonds and the shell composed of eight surrounded organic groups, which may be designed according to needs. The inner diameter of POSS is about 0.53 nm and the outer diameter is generally between 1 nm and 3 nm due to different organic functional groups. POSS has regular structure, good biocompatibility, small scale and large surface area, which make POSS as one of the most potential next generation biomaterials. POSS macromers with different shells have been doped into polystyrene [24], PMMA [25], [26], polyurethane [27], polyethylene [28], ethylene–propylene [29], etc. by the way of copolymerization with other polymer monomers to change its mechanic, thermodynamic, surface or biological properties. Previous study [25] found that POSS and polymer hybrid is capable of forming a colorless transparent material, which does not affect the light transmittance. The cytotoxicity of POSS was also investigated and it was found that the toxicity of POSS is very low, almost non-toxic. Therefore, POSS nanomaterial is more suitable than other materials for ophthalmology biological repair alternatives. However, there is almost no reference about the studies on POSS used for IOL modification.

In order to improve the biocompatibility of PMMA used as IOL material and achieve the rapid epithelialization, surface characteristics of PMMA can be changed through bulk modification. In this work, polymer of allyl POSS–PMMA was prepared using radical random copolymerization method. A schematic of the synthesis procedure is presented in Scheme 1. The number-average molecular weight (Mn) and weight-average molecular weight (Mw) of allyl POSS–PMMA copolymer and PMMA were measured by gel permeation chromatography (GPC). The effect of POSS on the crystallization, thermodynamic properties, optical performance and surface properties of allyl POSS–PMMA were studied in detail with various techniques. Furthermore, cell viability assay was performed to determine biocompatibility of the allyl POSS–PMMA copolymer with HLECs by fluorescein diacetate (FDA) and Cell Counting Kit-8 (CCK-8) methods.

Section snippets

Materials and reagents

Isobutyl (allyl)-POSS(R), [(allyl)(isobutyl)7Si8O12] (allyl POSS) from Hybrid Plastics Co. and methyl methacrylate (MMA), azobisisobutyronitrile (AIBN), ethyl acetate, ethanol and tetrahydrofuran (THF) from Aldrich were used as received.

Synthesis of allyl POSS–PMMA copolymers

Allyl POSS–PMMA copolymers containing 0.01 or 0.02 weight of the allyl POSS monomers have been synthesized by free-radical polymerisation. The typical synthesis process (0.02 allyl POSS–PMMA) is described as follows: in a 50 mL round bottom flask, allyl POSS (0.34

Synthesis of allyl POSS–PMMA copolymers

The allyl POSS–PMMA copolymer was synthesized via free radical polymerization using AIBN as the initiator, allyl POSS and MMA as monomers. The successful synthesis of copolymers was proved by 1H NMR. Fig. 1. is the typical 1H NMR spectra of 0.02 allyl POSS–PMMA copolymer recorded in CDCl3 with the relevant signals labeled. The characteristic resonance signals at 0.60 ppm, 0.91 ppm, 1.81 ppm, and 1.85 ppm were attributed to allyl POSS, while signals at 0.85 ppm, 1.03 ppm, 1.25 ppm, 1.60 ppm and 3.60 ppm

Conclusion

Allyl POSS–PMMA copolymer was synthesized by radical polymerization and made into film as IOL material. FT-IR, XRD and 1H NMR measurements indicated the successful synthesis of allyl POSS–PMMA copolymer. By incorporating of ally POSS into the PMMA main chain results in good thermodynamic properties and high transparency of PMMA-based polymeric material. Characterizations of morphology and surface hydrophility suggested that the allyl POSS–PMMA copolymer film had a higher hydrophobicity and a

Acknowledgments

Financial supports from National Natural Science Foundation of China (81271703, 51203120), Natural Science Foundation of Zhejiang Province (LQ12E03001), Medical & Health Technology Program of Zhejiang Province (2013KYA133, 2014KYA149), the International Scientific and Technological Cooperation Projects (2012DFB30020) and the Specialized Research Fund for Science and Technology Major Projects of Higher Education of China (ZD2007006) are greatly acknowledged.

References (43)

  • J.W. Cheng et al.

    Am. J. Ophthalmol.

    (2007)
  • N. Li et al.

    Ophthalmology

    (2008)
  • D.M. Saylor et al.

    Acta Biomater.

    (2010)
  • S. Sacu et al.

    J. Cataract Refract. Surg.

    (2004)
  • B. Amoozgar et al.

    Coll. Surf. B

    (2013)
  • S.M. Shah et al.

    J. Cataract Refract.

    (1995)
  • O. Findl et al.

    Ophthalmology

    (2005)
  • R.J. Linnola

    J. Cataract Refract.

    (1997)
  • R.A. D’Sa et al.

    J. Colloid Interface Sci.

    (2012)
  • M.J. Yang et al.

    J. Colloid Interface Sci.

    (2012)
  • X.D. Huang et al.

    J. Cataract Refract.

    (2010)
  • L. Lin et al.

    Appl. Surf. Sci.

    (2010)
  • S.H. Phillips et al.

    Interface Sci.

    (2004)
  • R.Y. Kannan et al.

    Biomaterials

    (2006)
  • Y. Yani et al.

    Polymer

    (2009)
  • S.S. Li et al.

    J. Colloid Interface Sci.

    (2013)
  • B. Cortese et al.

    J. Colloid Interface Sci.

    (2013)
  • Z. Zheng et al.

    Biomaterials

    (2005)
  • Z.W. Dai et al.

    Biomaterials

    (2009)
  • L.H. Zhang et al.

    Appl. Surf. Sci.

    (2009)
  • B.L. Wang et al.

    Appl. Surf. Sci.

    (2012)
  • Cited by (42)

    • Modified POSS nano-structures as novel co-initiator-crosslinker: Synthesis and characterization

      2021, Dental Materials
      Citation Excerpt :

      As Fig. 6(a) shows, BT has the highest water sorption, and BTP3 shows the least. Replacing the AMA-POSS nanostructures instead of DMAEMA, water uptake decreased (p < 0.05) significantly because of the hydrophobic nature of silsesquioxane cage [45]. Because of with the small quantity of the AMA-POSSs (BTP8, BTP6, BTP3), no significant differences were observed between the water uptakes of the specimens.

    • Bioactive response of PMMA coating obtained by electrospinning on ISO5832-9 and Ti6Al4V biomaterials

      2021, Surface and Coatings Technology
      Citation Excerpt :

      The surface becomes positively charged therefore attracting negatively charged hydroxyl groups and consequently functionalizing it. These radicals presence on PMMA surface can impose and/or improve bioactivity to the polymeric surface [10,22,38]. In our previous paper [22] it was shown by chromatography curves that the EISA process induces formation of active OH- group by scissioning the PMMA chain.

    • Inhibition of immunotoxicity of Pb<sup>2+</sup>-induced RAW264.7 macrophages by selenium species in selenium-enriched rice

      2021, Food and Chemical Toxicology
      Citation Excerpt :

      Cells were cultured in DMEM medium containing 10% FBS and 1% penicillin/streptomycin at 37 °C in humidified 5% CO2 atmosphere. Then, the cell viability of (Pb2+)-induced RAW264.7 cells was measured using CCK-8 assay (Wang et al., 2014). Cells (1×105 cells/mL) were cultured in 96-well plates at 37 °C and 5% (v/v) CO2 for 24 h.

    View all citing articles on Scopus
    View full text