Hyaluronic Acid based Therapeutic Bandage Contact Lenses for Corneal Wound Healing
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abstract
The cornea is an avascular transparent tissue exposed to the environment and therefore highly susceptible to damage. With an increase in corneal refractive surgeries, corneal transplants, and corneal injuries, understanding and improving corneal healing mechanisms are extremely important. Impaired healing of corneal wounds can lead to decreased visual acuity and extreme pain. Serum eye drops, amniotic membranes, pharmaceutical agents, biopolymers, and cell transplants are just a few approaches that have been employed to improve wound healing. Bandage contact lenses (BCLs) have been proposed as a simple method to facilitate wound healing while reducing pain. The synthesis of a silicone hydrogel contact lens capable of surface binding hyaluronic acid (HA) for corneal wound healing was explored in the current work. HA was used as both a wetting agent and a therapeutic.
The work presented describes the synthesis, characterization, and cell testing of the HA binding model silicone hydrogels, composed of the hydrophilic monomer, 2-hydroxyethyl methacrylate (HEMA) and a hydrophobic silicone monomer, methacryloxypropyltris (trimethylsiloxy) silane (TRIS). Three different methods were evaluated for increasing HA binding and improving surface wettability.
“Caged lenses” utilized the same base polymer with the incorporation of methacrylated N-Hydroxysuccinimide (NHS). Hydrophilic polyethylene glycol (PEG) chains were then tethered from the NHS, forming a “cage” with the potential to physically entrap HA. Although surface wettability was improved, less HA was entrapped in the caged lenses compared to model silicone hydrogels, presumably due to the increased hinderance resulting from the PEG chains.
“Tethered HA” lenses utilized PEG as a spacer to conjugate HA to the lens surface in order to improve surface hydrophilicity. Methacrylated HA conjugation resulted in a significant decrease in contact angle (p <0.01) compared to model pHEMA-co-TRIS whereas tethered thiolated HA did not lead to a significant decrease (p >0.05) in contact angle. It was clear that neither of these methods would lead to sufficient HA binding.
Ionic interaction lenses utilize monomers and small molecules that contain a positive charge to bind to the negatively charged HA under physiological conditions. The monomer diethylaminoethyl methacrylate (DEAEM) was polymerized directly into the polymer backbone, but resulted in no significant decrease (p >0.05) in contact angle. In comparison, surface functionalization using thiolene “click” chemistry allowed conjugation of the small molecule, dimethylamino ethanethiol (DMAET) and diethylamino ethanethiol (DEAET). DMAET and DEAET modified lenses showed significantly higher (p <0.001) HA binding compared to model pHEMA-co-TRIS controls at all time points. The modified lenses improved release kinetics preventing an initial burst release and showed consistent release when unloaded and reloaded with HA. The contact angle was significantly decreased (p <0.05) for the modified lenses with HA without affecting the equilibrium water content. Optical transparency was reduced following lens modifications although the thickness of the disks prepared was higher than a typical contact lens. Finally, the modified lenses did not exhibit any cytotoxicity in vitro with human corneal epithelial cells (HCECs).
The synthesis of silicone hydrogels capable of surface binding HA have potential to be used as a bandage contact lens while improving surface wettability and enhancing comfort.
