**2. Applications**

#### *2.1. Compatibility and Reactivity Introduction*

The living polymerization of siloxanes provides the basis for synthesizing siloxane macromers capable of acting as precise structural elements, achieving both the requirements of copolymerization with organic monomers as well as the desired properties of copolymers. The incorporation of properties associated with siloxanes—including oxygen and moisture permeability, release, or thermal performance—would thereby improve the performance of a wide range of organic polymers. To date, however, the utilization of silicone macromers in combination with organic monomers has been primarily limited by economic considerations, as well as by structural and compositional challenges.

The most commonly used siloxane macromers are methacrylate-terminated, both in the literature and in commercial applications. Reported reactivity ratios [79] and previously unreported solubility in monomers are shown in Tables 5 and 6, respectively


**Table 5.** Reactivity Ratios of Methacrylate Functional Siloxane Macromers.

\* Rate constants—M1M1/M1M2: M2M2/M2M1; \*\* no meaningful results.


\* Author's work, previously unreported.

#### *2.2. Gas/Vapor Permeability*

In comparison to organic polymers, siloxanes possess a large free molal volume, a consequence of the length of both silicon–oxygen and silicon–carbon bonds, which allows greater permeation of small molecules. These same factors contribute to the flexibility of silicones which imposes limitations on structural properties. Hybrid polymer systems utilizing both macromer and block polymers generated by living AROP provide the balance of properties required in contact lenses, breathable films, and membranes.

#### 2.2.1. Contact Lens/Hydrogel

Oxygen permeability is a key feature of modern contact lenses, particularly those intended for extended wear. In addition to the bloodstream, the corneal and scleral tissues of the eye take about 1/3 of their respiratory requirement directly from the air. Methacrylatederived polymers, while possessing good optical and mechanical properties, are occlusive to oxygen transport due to the fact that the permeability of siloxanes is more than 100X greater than that of analogous hydrocarbon structures. Gaylord's pioneering material work [117,118] under the direction of Seidner led to the commercialization of rigid gas permeable contact lenses by Syntex in 1980 [119]. While these lenses satisfied the physiological requirement for extended wear, broad acceptance of silicone rigid gas permeable (RGP) lenses was not achieved, since user comfort did not match that of hydrogel lenses. Formulation and process challenges in silicone hydrogel contact lens manufacture include combining hydrophobic silicones with hydrophilic monomers while maintaining optical clarity, high water content, and high oxygen transport to the eye in the resulting hydrogels. The first successful silicone hydrogel lens, based on technology disclosed by Vanderlaan, was introduced to the marketplace by Vistakon in 2004 [102]. Monofunctional siloxane macromers polymerized by living anionic polymerization routes are key materials in such silicone hydrogel contact lens formulations: these monodisperse monofunctional materials are used as comonomers with hydrophilic hydrogel monomers such as hydroxyethylmethacrylate (HEMA) and dimethylacrylamide (DMA). The earliest report of soft silicone hydrogel lenses generated from siloxane macromers and HEMA that displayed acceptable performance utilized group transfer polymerization [120]. One material requirement of a silioxane macromer selected for such a formulation is a minimal solubility in the hydrophilic hydrogel monomers. It has been reported that, after curing the silicone hydrogel contact lens reactive monomer mix, an optically clear co-continuous silicone and hydrogel phase membrane suitable for contact lens use is formed [121]. Incorporating low molecular weight (~1000 g mol−1) siloxane macromers into silicone hydrogel formulations enhances oxygen permeability in the resulting contact lenses, achieving superior oxygen transport to the eye compared to hard rigid gas permeable (RGP) and soft HEMA contact lens technologies (Figure 4) [122].

**Figure 4.** (**a**) Silicone hydrogel lenses incorporate low MW macromers into otherwise hydrophilic matrices based on hydroxyethylmethacrylate or dimethylacrylamide; (**b**) comparison of contact lens materials and oxygen transport to the cornea (redrawn with permission from Ref. [122] Copyright 1983 the Technomic Publication). (**c**) Hydrogel phase structure as a determinant of lens comfort (redrawn with permission from Ref. [121] Copyright 2001 Elsevier Science).

During the contact lens molding process, extraction procedures are employed to remove undesirable impurities. Water insoluble impurities, for example, decrease optical clarity and leach out of the contact lens, causing negative ocular effects such as stinging [92]. Unfortunately, the hydrophobic nature of these impurities makes conventional water extraction procedures insufficient. Silicone hydrogel extraction procedures using alcohols have been reported, but possess drawbacks including increased manufacturing costs, organic solvent waste handling concerns, and potential eye irritation from residual solvent. Living anionic polymerization enables the synthesis of monodisperse monofunctional siloxane macromers that are largely free of impurities. Indeed, newer generation silicone hydrogel formulations employ siloxane macromers of sufficient purity to rely solely on aqueous extraction and hydration steps post-molding. Table 7 gives an overview of the different generations of silicone hydrogel technologies. Generation 1 silicone hydrogel contact lenses did not use siloxane macromers and relied on tris(trimethylsilyl)-silylpropylmethacrylate (TRIS) and difunctional silicone crosslinkers as the oxygen transport enhancers in the formulation. TRIS made control of the lenses' mechanical properties difficult, resulting in higher modulus lenses that were not comfortable for the wearer [121]. Generation 2 and

3 silicone hydrogel formulations incorporated siloxane macromers as oxygen transport enhancers, which led to greater formulation flexibility and control of the final contact lens material properties (e.g., Dk and modulus) [100,101,123].


**Table 7.** Silicone Hydrogel Contact Lens Technology.

\* DMA—Dimethylacrylamide; DMPC—(1,2-dimyristoyl-sn-glycero-3-phosphocholine; HEMA—Hydroxyethylmethacrylate; NVP—N-Vinylpyrrolidone; PVP—Polyvinylpyrrolidone; SiGMA—3-(3-Methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane; TRIS—Methacryloxypropyltris(trimethylsiloxy)silane; VMA—N-Vinylmethylacetamide.

> Hydrogels comprised of macromers with both polycarbosiloxane units and poly(trifluoropropylmethyl)siloxane units have been reported. The macromers are synthesized by substituting D3 with other ring-strained monomers in a living polymerization process. Awasti describes a monomethacrylate functional polycarbosiloxane synthesized from a 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane monomer as resistant to hydrol

ysis and therefore suitable for use in silicone hydrogel soft contact lens design [55,128]. Monomethacrylate functional poly(trifluoropropylmethyl)siloxane macromers possess increased polarity, improving their miscibility with hydrophilic monomers and potentially reducing the non-specific binding of proteins on soft contact lens surfaces [59,70].

Low molecular weight symmetric siloxane macromers with hydrophilic termini have increased miscibility with hydrophilic monomers compared to asymmetric siloxane macromers, as the smaller siloxane block size of the symmetric architecture limits phase separated domain formation while still maintaining the oxygen transport-enhancing benefits of asymmetric analogs. The hydrophilic termini reported by Kimble include methoxypropyl and hydroxypropyl groups [59,60]. α-Methacrylate functional, ω-polyalkyleneoxide siloxane macromers have also been described; however, their block copolymer structure results in microphase separation, rendering this macromer structure unsuitable for the production of optically clear hydrogel films [129].

One approach for improving contact lens comfort is to utilize a plasma treatment to improve hydrogel wettability and then apply hydrophilic terpolymers derived from combinations of silicone macromers and hydrophilic monomers such as diethylazetidinium methacrylate ester chloride salt, thereby providing permanent wettability [130].

In a separate but related area, siloxane-based interocular lenses (IOL) provide new opportunities for macromers. Hydride terminated macromers are utilized to control the modulus of cured elastomers used in IOLs [131]. Interestingly, silicone macromers are broadly described as components in laser adjustable IOLs that enable a post-insertion change in dioptric power by altering the refraction of the lens material [132].

Independent of contact lens development, optically clear films were derived from copolymers of styrene, ethylene glycol dimethacrylate (EGDMA), and siloxane-urethanemethacrylate (SiUMA). The SiUMA monomer was synthesized from carbinol-terminated siloxane macromers reacted with isocyanatoethylmethacrylate [133].

#### 2.2.2. Controlled Atmospheric Packaging—Modified Atmosphere Packaging

An appreciation of the role that gases play in maintaining the freshness of meats, fruits, and vegetables during transport has created a role for polymer films with controlled permeability. Optimal oxygen concentration is associated with the appearance of "red" meat and "green" vegetables. In the case of meat, deoxymyoglobin, which is purple, forms when metabolic, diffusion, and other processes deplete oxygen availability. Over time, however, oxymyoglobin is oxidized to amber-brown methemoglobin, which is associated with a lack of freshness [134]. Ethylene is associated with fruit ripening and abscission. Gas permeable films derived from acrylate terpolymers act as overlayers to porous structures, maintaining the oxygen transmission of these structures while providing a barrier to microbial infiltration. Unlike in the case of contact lenses, transparency is usually not required for packaging applications. The use of higher molecular weight monomethacrylate macromers in packaging is therefore acceptable, and has been reported [135]. Breathable films based on this technology have become components in commercial packaging applications offered by BreatheWay, as shown in Figure 5.

**Figure 5.** Breathable films and packaging (Reprinted courtesy of Breathway Corp).
