Functionalised polysiloxanes as injectable, in situ curable accommodating intraocular lenses

Abstract

The aged eye's ability to change focus (accommodation) may be restored by replacing the hardened natural lens with a soft gel. Functionalised polysiloxane macromonomers, designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via a twostep synthesis. Prepolymers were synthesised via ring opening polymerisation (ROP) of octamethylcyclotetrasiloxane (D 4 ) and 2,4,6,8-tetramethylcyclotetrasiloxane (D 4 H ) in toluene using trifluoromethanesulfonic acid (TfOH) as catalyst. Hexaethyldisiloxane (HEDS) was used as the end group to control the molecular weight of the prepolymers, which were then converted to macromonomers by hydrosilylation of the SiH groups with allyl methacrylate (AM) to introduce polymerisable groups. The resulting macromonomers had an injectable consistency and thus, were able to be injected into and refill the empty lens capsular bag. The macromonomers also contained a low ratio of polymerisable groups so that they may be cured on demand, in situ, under irradiation of blue light, in the presence of a photo-initiator, to form a soft polysiloxane gel (an intraocular lens) in the eye. The pre-cure viscosity and post-cure modulus of the polysiloxanes, which are crucial factors for an injectable, in situ curable A-IOL application, were controlled by adjusting the end group and D 4 H concentrations, respectively, in the ROP. The macromonomers were fully cured within 5 minutes under light irradiation, as shown by the rapid change in modulus monitored by photorheology. Ex vivo primate lens stretching experiments on an Ex Vivo Accommodation Simulator (EVAS) showed that the polysiloxane gel refilled lenses achieved over 60% of the accommodation amplitude of the natural lens. An in vivo biocompatibility study in rabbits using the lens refilling (Phaco-Ersatz) procedure demonstrated that the soft gels were biocompatible with the ocular tissue. The polysiloxane macromonomers meet the targeted optical and mechanical properties of a young natural crystalline lens and show promise as candidate materials for use as injectable, in situ curable A-IOLs for lens refilling procedures.

Biomaterials for ocular reconstruction

“…These gels could replace conventional IOLs, and perhaps the incidence of PCO, as the gel fills the irregularly shaped lens capsule eliminating space for cell proliferation and migration. These gels also offer similar refractive index and mechanical properties to the native lens meaning the gel could allow for accommodation of focus on closer objects, which naturally degrades with age resulting in the need for reading glasses [83,85]. In previous years, however, there have been concerns over toxicity associated with leakage of unreacted monomer [85].…”

“…The capsular bag is filled with a gel that sets at body temperature [83][84][85]. These gels could replace conventional IOLs, and perhaps the incidence of PCO, as the gel fills the irregularly shaped lens capsule eliminating space for cell proliferation and migration.…”

“…More recent research has investigated the use of hydrogel and siloxane polymers that can be cross-linked in order to prevent leakage of unreacted monomer [84] investigating the use of a polysiloxane gel that was curable in situ. Hexaethyldisiloxane was used to control the molecular weight and induced polymerisable groups which meant that the gels could be cured using blue light [83]. Annaka et al investigated an accommodating IOL based on hydrophobically modified poly(ethylene glycol) (HM-PEG), containing silica nanoparticles to increase the refractive index and mimic the optical and mechanical properties of a young natural lens.…”

Synthesis of phenyl silicone resin with epoxy and acrylate group and its adhesion enhancement for addition-cure silicone encapsulant with high refractive index

“…The signals of the protons of epoxy group are detected at 2.5, 2.7, and 3.1 ppm [26]. The signal of the protons of CH 2 =C-CH 3 is detected at 1.9 ppm [27]. The signals at 0.5, 1.6, and 4.0 ppm are assigned to the protons of -COO-CH 2 -CH 2 -CH 2 -, -COO-CH 2 -CH 2 -, and -COO-CH 2 -, respectively [28].…”

Surface modification of silicone via colloidal deposition of amphiphilic block copolymers

“…Silicone ( poly(dimethylsiloxane), PDMS) artefacts are often employed for biomedical use in the form of medical devices 1 such as intraocular lenses, 2 urinary catheters 3 and breast implants, 4 but also microfluidic constructs; 5 in their application they are often in contact with biological fluids, and the ensuing surface adsorption of proteins may lead to undesired outcomes, which in vivo can take the form of foreign body capsular reactions or of phenomena of platelet adhesion/activation. 6,7 Another disadvantage of PDMS surfaces is the possibility of bacterial attachment, leading to the formation of biofilms, which are among the first promoters of chronic infections.…”