Biogel Release to the Ocular Surface of Epithelial Growth Factors Mid-Semester Report May 5, 2010 Team Members John Byce: Co-Leader Sarah Reichert: Co-Leader Anthony Sprangers: Communicator Jeff Hlinka: BWIG Alex Johnson: BSAC Client Dr. Neal Barney Advisor Professor Christopher Brace2 Abstract Dry eye is an affliction that results from an imbalance in the tear-flow system of the eye. Although there are treatment options currently available, they mainly function to reduce discomfort and are incapable of repairing epithelial cell damage. Therefore our client, Dr. Neal Barney, proposed that we design and fabricate a new treatment option that involves the extended release of growth factors from a biogel. Through research, we discovered three gels that could potentially be used for this application; poly(ethylene glycol) hydrogels, collagen shields, and poloxamer hydrogels. Based on the results of our design matrix, we chose to pursue the poly(ethylene glycol) hydrogel for our final design. After creating this gel, we performed various tests to determine the amount of swelling, the rate of degradation, and cytotoxicty to a cell culture. The results were that it swells to 200% its initial volume, degrades in 40 days at 20 °C, and does not cause cell death over two days of use (further testing of toxicity was unable to be obtained due to an infection of the cells).3 Table of Contents Abstract...........................................................................................................................................2 Background.....................................................................................................................................5 Current Treatments..........................................................................................................................7 Tear Supplementation..........................................................................................................7 Tear Retention.....................................................................................................................7 Tear Stimulation..................................................................................................................8 Biological Tear Substitutes.................................................................................................8 Anti-Inflammatory Therapy................................................................................................9 Problem Statement and Motivation.................................................................................................9 Design Requirements.....................................................................................................................10 Design Alternatives........................................................................................................................12 Poly(ethylene glycol) Hydrogel.........................................................................................12 Collagen Shields................................................................................................................13 Poloxamer Hydrogel..........................................................................................................15 Design Matrix................................................................................................................................17 Final Design...................................................................................................................................21 Growth Factors...............................................................................................................................22 Testing............................................................................................................................................23 Swelling.............................................................................................................................23 Degradation........................................................................................................................26 Live/Dead Assay................................................................................................................30 Costs...............................................................................................................................................334 Time Management.........................................................................................................................34 Future Work...................................................................................................................................35 Physiologic Conditions......................................................................................................35 Diffusion Testing...............................................................................................................36 Drug Delivery Vehicle.......................................................................................................37 Clinical Testing..................................................................................................................38 References......................................................................................................................................39 Appendix........................................................................................................................................415 Background Keratoconjunctivitis, commonly known as dry eye, is a disorder of the tear film caused by abnormal evaporation or deficient production of tears on the ocular surface. This condition results in the damaging of the corneal epithelium as well as symptoms of discomfort1. Dry eye disease can be divided into two major categories, Aqueous Deficient Dry Eye and Evaporative Dry Eye. Aqueous Deficient Dry Eye (ADDE) refers to symptoms onset by insufficient production of lacrimal tears. ADDE can also result from a lack of water secretion by the conjunctiva, the membrane that lines the eyelids. Two subclasses of ADDE, Sjögren Syndrome and Non-Sjögren Syndrome Dry Eye, underline the causative mechanisms responsible for the insufficient tear production2. Sjögren Syndrome is defined as an autoimmune disease causing white blood cells to attack vital moisture-producing glands, such as the lacrimal and salivary glands. This autoimmune
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