Scott Fitzpatrick

Efficient delivery of therapeutic cell and pharmaceutical suspensions to the posterior segment of the eye remains an elusive goal. Delivery is made difficult by blood ocular barriers that separate the eye from systemic circulation, the compartmentalized structure of the eye that limits diffusion across the globe, and effective clearance mechanisms that result in short drug residence times. The work presented

ABSTRACT Posterior capsule opacification is the most common complication of cataract surgery. Lens epithelial cells remaining in the capsular bag following surgery can undergo epithelial-to-mesenchymal transition and migrate from the anterior to the posterior capsule, leading to fibrosis, capsular wrinkling, and ultimately vision loss. Transforming growth factor-beta 2 has been shown to play a major role in epithelial-to-mesenchymal transition. Covalent tethering of anti-transforming growth factor-beta 2 to the surface of the intraocular lens material may inhibit epithelial-to-mesenchymal transition and the subsequent events, thus leading to a reduction in posterior capsule opacification. In this work, the antibody was tethered to the surface of polydimethylsiloxane as a model lens material via a poly(ethylene) glycol spacer. Surface characterization using a variety of methods demonstrated successful modification. The surface density of the anti-transforming growth factor-beta 2 was approximately 0.5 μg/cm2. The presence of transforming growth factor-beta 2 in cell culture medium stimulated production of extracellular matrix components such as collagen, fibronectin, laminin, and the fibrotic marker α-smooth muscle actin, by HLE-B3 cells. These effects were decreased but not completely eradicated by the presence of the anti-transforming growth factor-beta 2 antibody on the polydimethylsiloxane surface. These results suggest that surface modification with appropriate antifibrotic molecules has the potential to modulate cellular changes following cataract surgery and lead to a reduction in posterior capsule opacification.

Responsive polymer systems that react to thermal and light stimuli have been a focus in the biomaterials literature because they have the potential to be less invasive than currently available materials and may perform well in the in vivo environment. Natural and synthetic polymer systems created to exhibit a temperature-sensitive phase transition lead to in situ forming hydrogels that can be degradable or non-degradable. These systems typically yield physical gels whose properties can be manipulated to accommodate specific applications while requiring no additional solvents or cross-linkers. Photo-responsive isomerization, dimerization, degradation, and triggered processes that are reversible and irreversible may be used to create unique gel, micelle, liposome, and surface-modified polymer systems. Unique wavelengths induce photo-chemical reactions of polymer-bound chromophores to alter the bulk properties of polymer systems. The properties of both thermo- and photo-responsive polymer systems may be taken advantage of to control drug delivery, protein binding, and tissue scaffold architectures. Systems that respond to both thermo- and photo-stimuli will also be discussed because their multi-responsive properties hold the potential to create unique biomaterials.