Abstract
Purpose: :
The purpose of this study is to develop a hydrogel bandage contact lens system suitable for prolonged delivery of thymosin beta 4 (TB4) to the corneal epithelium.
Methods: :
Crosslinked PEG di-acrylate (PEGDA) hydrogels were prepared from PEGDA of Mw 700 Da and 575 Da. Similarly, calcium-crosslinked alginate hydrogels were prepared at a range of concentrations. Values for the average Mw between crosslinks were determined by equilibrium swelling studies, and the binding and diffusion of TB4 to and through candidate hydrogels were characterized using both unmodified and fluorescently labeled TB4. In addition, cell migration studies were performed to test the effects of TB4 on cell migration speed, persistence and cell spreading. Briefly, immortalized human corneal epithelial cells (HCET) were seeded on collagen coated plates and grown for 7 days. Time lapse video microscopy was used to characterize cell migration speed, persistence time and net displacement.
Results: :
The results from the hydrogel studies confirm the potential for extended release of TB4 greater than 100 hours from the PEGDA hydrogels. The effect of this on TB4 diffusion was seen in binding and diffusion studies. Studies aimed at optimizing TB4 release rates over 100 hours are currently ongoing, and results of the release studies and the biological activity of the release TB4 will be reported. In addition, cell migration results demonstrated a reduced persistence time, speed and cell spreading compared to controls. The reduced spreading observed suggests a shift toward a migratory phenotype. However, decreased net displacement suggests an increased localized deposition of matrix consistent with previous observations.
Conclusions: :
These results demonstrate that we have developed a platform that can be optimized for delivery of TB4 to the damaged corneal surface. Building upon our previous studies indicating that TB4 promotes corneal wound healing and decreases inflammation, the data herein suggest that further studies to develop a TB4-bandage contact lens as a novel therapeutic delivery device appear feasible.
Keywords: wound healing • cornea: epithelium • contact lens