Surface Modification of Silicone Intraocular Implants To Inhibit Cell Proliferation Paolo Yammine, Graciela Pavon-Djavid, Gerard Helary,* and Veronique Migonney Laboratoire des Biomate ´ riaux et Polyme ` res de Spe ´ cialite ´ , UMR 7052, Universite ´ Paris 13, Avenue Jean Baptiste Cle ´ ment, 93 430 Villetaneuse, France Received April 11, 2005 Photo-cross-linkable polymers bearing cinnamic, sulfonate, and carboxylate groups were synthesized by radical polymerization leading to randomly distributed copolymers. These polymers were used to coat silicone intraocular lenses in order to reduce posterior capsule opacification, also named “secondary cataract”. We previously demonstrated that polymers containing both carboxylate and sulfonate groups inhibit cell proliferation, and formulations with the ratio R ) COO - /(COO - + SO 3 - ) equal to 0.64 provided the highest inhibitory effect. Ionic polymers with this formulation were synthesized to contain a monomer with pendant siloxane groups in order to get compatibility with the silicone matrix of the intraocular lenses. Anchorage of the ionic polymer at the surface of the silicone implant was achieved by a cycloaddition reaction of the photosensitive groups according to two options. These modified silicone surfaces grafted onto intraocular lenses were shown to inhibit cell proliferation to 60%. Introduction Posterior capsule opacification (PCO) or “secondary cataract” is a major problem associated with cataract surgery and intraocular lens (IOL) implantation. The incidence of this phenomenon remains as high as 50% after two years of follow-up. Considering the large number of cataract surgeries, PCO may generate important medical, social, and economic problems. The decrease of visual acuity is assumed to be provoked by the proliferation of remaining lens epithelial cells, both onto the IOL and on the inner face of the capsular bag. 1-3 During the last ten years, improvements in surgical techniques 4 as well as in IOL design 5-7 have shown progress in delaying the migration and proliferation of these cells, but PCO remains a challenging problem. One of the most important parameters in successful IOL application is the biocompatibility of the polymer used to manufacture the implant. Biocompatibility of various poly- mers, such as poly(methyl methacrylate), 8-10 silicone, 11,12 and hydrogels, 13,14 has been examined. IOLs with high hydro- phobic or hydrophilic surface properties have been shown to induce decreases in cell adhesion and proliferation. 15-17 Preparation of such materials has been achieved by different methods, including polymerization or copolymerization of appropriate monomers (hydrophilic or hydrophobic), 18-20 plasma treatment, 21,22 and deposition of hydrophilic or hydrophobic coatings. 20,23,24 However, until now, modified IOLs have not been successful in preventing in vivo cell adhesion and prolifera- tion. This is believed to arise from a hostile host response toward the foreign body IOL consisting of nonspecific protein adsorption, inflammatory reaction, dedifferentiation of remnant or regenerated epithelial cells into fibroblasts, cell migration, and proliferation. Several groups have targeted functionalization of surfaces with biological molecules in order to control cell adhesion, signaling, and function. 25,26 Another proposed way to prevent PCO consists of control- ling cell proliferation by orienting the intracellular signaling through the control of adhesive proteins/cell receptor interac- tion. Recently, we have shown that poly(methyl methacry- late) (PMMA)-based copolymers bearing randomly distrib- uted sulfonate and carboxylate groups inhibit fibroblast and epithelial cell proliferation. 18,27 The highest inhibiting proper- ties, ∼70%, were observed for random copolymers bearing equivalent amounts of sulfonate and carboxylate groups. The aim of this work was to synthesize a bioactive polymer bearing sulfonate and carboxylate groups randomly distrib- uted and to graft it on silicone intraocular lenses. Indeed, silicone is a good candidate for IOL application because of its high flexibility, allowing folding and minimal incision for implant insertion. Moreover, silicone implants present good optical properties, oxygen permeability, and chemical stability. Appropriate copolymers for grafting onto silicone implants have to present appropriate physicochemical prop- erties such as optical transparency and chemical compatibility with the silicone matrix. These two requirements led us to choose tris(trimethylsiloxy)methacryloxy propyl silane (TT- MPS), a monomer with a silicone pendant group, which has been used to prepare rigid contact lenses. 28 Because polymers with pendant photosensitive groups such as cinnamoyl groups have been described as undergoing cross-linking upon UV irradiation, 29-32 we selected a photo- cross-linking reaction to bind the bioactive copolymer at the surface of the silicone implant. To obtain a network at the surface of silicone lenses (Figure 1), we introduced a * Correspondence should be addressed to Gerard He ´lary, Laboratoire des Biomate ´riaux et Polyme `res de Spe ´cialite ´, Universite ´ Paris 13, Avenue Jean Baptiste Cle ´ment, 93430 Villetaneuse. ghelary@galilee.univ-paris13.fr. 2630 Biomacromolecules 2005, 6, 2630-2637 10.1021/bm058010l CCC: $30.25 © 2005 American Chemical Society Published on Web 08/16/2005