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Access Type

WSU Access

Date of Award

January 2011

Degree Type

Thesis

Degree Name

M.S.

Department

Biomedical Engineering

First Advisor

Howard W. Matthew

Abstract

Thymosin beta-4 (Tb4, Mw = 4.9 kDa) is a naturally occurring and highly conserved actin-binding protein that has been shown to promote corneal epithelial cell migration in vitro and to accelerate corneal wound healing in vivo. Conditions such as diabetes mellitus, which affects 16 million Americans, are associated with impaired wound healing in many tissues. In particular, clinical therapies that re-establish normal corneal healing are extremely limited. Towards this end, we aimed to develop a hydrogel system suitable for prolonged delivery of Tb4 to the corneal epithelium. 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. Preliminary results suggest that both hydrogel types are suitable for achieving extended release of Tb4, but hydrogel permeabilities and mechanics require optimization. Candidate materials were shown to have increasing Mw between crosslinks with decreasing material concentration. The effect of this on Tb4 diffusion was seen in binding and diffusion studies. The biological effect of Tb4 on the immortalized human corneal cell line (HCT) showed significant morphologic changes. Examination of HCTs treated with Tb4 showed increased laminin V deposition and cell bodies more characteristic of a migratory morphology than those which received no treatment. These finding suggest Tb4 released from the candidate hydrogel materials may be an excellent therapy to enhance corneal wound healing.