Dimitriya Bozukova

Imparting antifouling properties of poly(2-hydroxyethyl methacrylate) hydrogels by grafting poly(oligoethylene glycol methyl ether acrylate)

The antifouling properties of poly(2-hydroxyethyl methacrylate- co-methyl methacrylate) hydrogels were improved by the surface grafting of a brush of poly(oligoethylene glycol methyl ether acrylate) [poly(OEGA)]. The atom-transfer radical polymerization (ATRP) of OEGA (degree of polymerization = 8) was initiated from the preactivated surface of the hydrogel under mild conditions, thus in water at 25 degrees C. The catalytic system was optimized on the basis of two ligands [1,1,4,7,10,10-hexamethyl-triethylenetetramine (HMTETA) or tris[2-(dimethylamino)ethyl]amine (Me6TREN)] and two copper salts (CuIBr or CuICl). Faster polymerization was observed for the Me 6TREN/CuIBr combination. The chemical composition and morphology of the coated surface were analyzed by X-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy, contact angle measurements by the water droplet and captive bubble methods, scanning electron microscopy, and environmental scanning electron microscopy. The hydrophilicity of the surface increased with the molar mass of the grafted poly(OEGA) chains, and the surface modifications were reported in parallel. The antifouling properties of the coatings were tested by in vitro protein adsorption and cell adhesion tests, with green fluorescent protein, beta-lactamase, and lens epithelial cells, as model proteins and model cells, respectively. The grafted poly(OEGA) brush decreased the nonspecific protein adsorption and imparted high cell repellency to the hydrogel surface.

Antibacterial activity of poly(vinyl alcohol)-b-poly(acrylonitrile) based micelles loaded with silver nanoparticles

A new amphiphilic poly(vinyl alcohol)-b-poly(acrylonitrile) (PVOH-b-PAN) copolymer obtained by selective hydrolysis of well-defined poly(vinyl acetate)-b-poly(acrylonitrile) copolymer synthesized by cobalt mediated radical polymerization was used for the preparation of PVOH-b-PAN based micelles with embedded silver nanoparticles. The successful formation of silver loaded micelles has been confirmed by UV-vis, DLS and TEM analysis and their antibacterial activity against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and spore solution of Bacillus subtilis (B. subtilis) has been studied. PVOH-b-PAN based micelles with embedded silver nanoparticles showed a strong bactericidal effect against E. coli, S. aureus and P. aeruginosa and the minimum bactericidal concentration for each system (MBC) has been determined.

Biomechanical and optical properties of 2 new hydrophobic platforms for intraocular lenses.

Purpose To compare the biomechanical and optical properties of 2 new hydrophobic platforms and a series of commercially available foldable intraocular lenses (IOLs). Setting Center for Education and Research on Macromolecules, University of Liège, Liège, Belgium. Design Experimental study. Methods Eleven benchmark foldable IOLs (iPure, Podeye, Acrysof SN60WF, Envista MX60, Sensar AR40e, Tecnis ZCB00, Isert 251, AF‐1 YA‐60BB, Finevision, Acri.Tec 366D, and Ioflex) were tested by standard analytical methods for biomechanical, rheological, and optical investigations under identical conditions. Results With 1 exception, IOLs equilibrated in aqueous medium had a lower glass‐transition temperature, higher deformability, lower injection forces, and complete recovery of their initial optical properties after injection. Typical hydrophobic acrylic dry‐packaged IOLs required higher injection forces with high residual deformation and lost part of their initial optical quality after injection. Hydrophobic acrylic C‐loop, double C‐loop, and closed quadripod haptics applied optimum compression forces to the capsular bag with negligible optic axial displacement and tilt compared with plate haptics and poly(methyl methacrylate) haptics. Conclusions The combination of the C‐loop haptic and the bioadhesive glistening‐free material, which absorbs a predetermined amount of water, allowed for a biomechanically stable IOL. The same material used in association with a double C‐loop haptic design facilitated the perioperative manipulation and placement of the IOL in a smaller capsular bag without impairing the other biomechanical properties of a single C‐loop design. Financial Disclosure Dr. Pagnoulle has a proprietary interest in the GF material. Drs. Pagnoulle and Bozukova are employees of Physiol S.A. Dr. Jérôme has no financial or proprietary interest in any material or method mentioned.

Assessment of new-generation glistening-free hydrophobic acrylic intraocular lens material

PURPOSE: To determine the hydrophobic, antiglistening, and bioadhesiveness properties of a new polymer, GF raw material, and to determine the suitability of this material for use in intraocular lenses (IOLs). SETTING: University of Liege, Liege, Belgium. DESIGN: Experimental study. METHODS: Intraocular lenses made of the new hydrophobic acrylic material were tested and compared with reference acrylic materials. The stability of their polymer matrix was estimated by testing for glistenings. The relative surface hydrophobicity was quantified via contact‐angle measurements. The degrees of bioadhesiveness of the reference and test materials were assessed by in vitro porcine lens epithelial cell (LEC) culture. RESULTS: The glistening test showed that the new material had greater stability under worst‐case conditions than previous‐generation hydrophobic acrylic materials. The new polymer had the same hydrophobic properties as the hydrophobic Acrysof IQ SN60WF material; both materials were less hydrophobic than the hydrophobic Sensar AR40e material and more hydrophobic than the hydrophilic Ioflex IOL material. The in vitro bioadhesiveness tests showed that porcine LEC adhesion levels of the new material were intermediate with respect to those of the 2 reference hydrophobic materials. CONCLUSIONS: When equilibrated in aqueous medium, the new‐generation hydrophobic acrylic material reached a low water content at equilibrium, making it glistening free. The hydrophobicity and bioadhesiveness of the new raw material were comparable to those of state‐of‐the‐art reference materials; these properties may resist the formation of posterior capsule opacification. Financial Disclosure: Dr. Pagnoulle has a proprietary interest in the GF material. Drs. Pagnoulle, Gobin, and Bozukova are employees of Physiol S.A. Mme. V. Bertrand and Dr. Gillet‐De Pauw have no financial or proprietary interest in any material or method mentioned.

Biointerface multiparametric study of intraocular lens acrylic materials.

Purpose To compare hydrophilic and hydrophobic acrylic materials designed for intraocular lenses in a multiparametric investigation in a liquid environment to highlight their properties in terms of adhesion forces, lens epithelial cell (LEC) adhesion, and tissue response as indicators of the risk for posterior capsule opacification (PCO) development. Setting University of Liège, Liège, Belgium. Design Experimental study. Methods The hydrophobicity and surface adhesion force were assessed using contact‐angle and atomic force microscopy measurements. The bioadhesiveness of the disks and the tissue response were determined by in vitro experiments using bovine serum albumin and porcine LECs and by in vivo rabbit subcutaneous implantation, respectively. Results Increasing surface hydrophobicity led to a greater surface‐adhesion force and greater LEC adhesion. After 1 month, the rabbit subcutaneous implants showed a similar thin layer of fibrous capsule surrounding the disks without extensive inflammation. A layer of rounded cells in contact with disks was detected on the hydrophobic samples only. Conclusions Hydrophobic acrylic disks that have been associated with a reduced risk for PCO in clinical studies showed increased tackiness. Financial Disclosures Proprietary or commercial disclosures are listed after the references.

RGD surface functionalization of the hydrophilic acrylic intraocular lens material to control posterior capsular opacification.

Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patients age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development.

Hydrogel nanocomposites: a potential UV/blue light filtering material for ophthalmic lenses

Poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (poly(HEMA-co-MMA)) and ZnS hydrogel nanocomposites were prepared and characterized. The chemical composition of the inorganic nanoparticles was confirmed by X-ray diffraction, and the homogeneity of their distribution within the hydrogel was assessed by transmission electron microscopy. The influence of the content of ZnS nanoparticles on the optical performances of the nanocomposites was investigated by UV-Vis spectroscopy. The ability of the hydrogel nanocomposites to filter the hazardous UV light and part of the blue light was reported, which makes them valuable candidates for ophthalmic lens application. In contrast to the optical properties, the thermo-mechanical properties of neat poly(HEMA-co-MMA) hydrogels were found to be largely independent of filling by ZnS nanoparticles (≤2 mg/ml co-monomer mixture). Finally, in vitro cell adhesion test with lens epithelial cells (LECs), extracted from porcine lens crystalline capsule, showed that ZnS had no deleterious effect on the biocompatibility of neat hydrogels, at least at low content.

Evaluation of a class of polyurethane materials for intraocular lens manufacturing

Ophthalmic lenses are medical devices with considerable requirements in terms of optical, biomechanical and biological performance. There is limited number of materials used for their manufacturing, comprising mainly silicones and poly(meth)acrylates. This series of publications aims at investigating the applicability of thermoplastic polyurethane elastomers (TPU) for the manufacturing of ophthalmic lenses and examining the properties of the respective devices. This study is related to the synthesis of TPUs with chemical compositions that comprise chemically grafted filters for the hazardous-light. GC-MS, attenuated total reflectance Fourier transform infrared spectroscopy, and UV-vis spectroscopies confirmed the reaction completion and the beneficial effect of the filters on the light transmittance, respectively. Relatively high refractive index of the material was measured and allows for the manufacturing of thinner lenses. The contrast sensitivity determined for a model intraocular lens (IOL) was satisfactory. Few optical defects were, however, present on the model lens prepared by thermoplastic injection molding. The elasticity of the materials was evaluated in view to their potential applicability as foldable IOLs by determining their glass transition temperature and their Young modulus and measuring their shore A. The TPU materials demonstrated more bioadhesive character compared with a benchmark hydrophilic acrylic reference material, which is already used for IOL manufacturing.

Plasma Surface Fluorination of Hydrogel Materials-coating Stability and in Vitro Biocompatibility Testing

Plasma enhanced chemical vapor deposition has been tested for the formation of hydrophobic perfluorinated coating on the surface of hydrophilic poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) [poly(HEMA-co-MMA)] substrates, used for the fabrication of intraocular lenses (IOLs). The properties of the dry and hydrated surface modified by two plasma techniques, Radio-frequency (RF) and Microwave (MW), were investigated in parallel by contact angle measurements in the dry and hydrated state, X-ray photoelectron spectroscopy, and atomic force microscopy. The coating stability and hydrophobicity were challenged by swelling and sterilizing the samples in water. Investigation of the optical performances of the modified samples was performed by ultraviolet spectroscopy and diopter measurements. Since materials with biomedical application are considered, the performances of their surface in contact with lens epithelial cells were tested at in vitro conditions, and repulsion was not found to be enhanced upon modification. Generally, the results showed poor stability of the coating and bring in question its covalent grafting to the surface.

Bioactive Intraocular Lens – A Strategy to Control Secondary Cataract

Cataract is the opacity of the lens, causing impairment of vision or even blindness. Today, a surgery is still the only available treatment. The intraocular lens (IOL) is a polymer implant designed to replace the natural lens in the cataract surgery. However, the bioinert materials could not satisfy the unmet need in the secondary cataract control. Posterior capsular opacification (PCO, or Secondary Cataract), characterized by a thick and cloudy layer of lens epithelial cells (LECs), is the most common postoperative complication.