Biogel Release to the Ocular Surface of Epithelial Growth Factors Mid-Semester Report March 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 have chosen to pursue the poly(ethylene glycol) hydrogel for our final design.3 Table of Contents Abstract...........................................................................................................................................2 Background.....................................................................................................................................4 Current Treatments..........................................................................................................................6 Tear Supplementation..........................................................................................................6 Tear Retention.....................................................................................................................6 Tear Stimulation..................................................................................................................7 Biological Tear Substitutes.................................................................................................7 Anti-Inflammatory Therapy................................................................................................8 Problem Statement and Motivation.................................................................................................8 Design Requirements......................................................................................................................9 Design Alternatives........................................................................................................................11 Poly(ethylene glycol) Hydrogel.........................................................................................11 Collagen Shields................................................................................................................12 Poloxamer Hydrogel..........................................................................................................14 Design Matrix................................................................................................................................16 Growth Factors..............................................................................................................................20 Future Work...................................................................................................................................22 Testing................................................................................................................................22 General...............................................................................................................................23 Projected Costs..................................................................................................................23 References......................................................................................................................................25 Appendix.......................................................................................................................................274 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 discomfort 1. 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. Two subclasses of ADDE, Sjögren Syndrome and Non-Sjögren Syndrome Dry Eye, underline the causative mechanisms responsible for the insufficient tear production 2. 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 response is further classified into primary and secondary Sjögren Syndrome. Primary refers to the presence of a sole autoimmune disease affecting the tear film production, whereas secondary refers to the coupling of primary Sjögren Syndrome with another autoimmune disease 3. Non-Sjögren Syndrome Dry Eye is insufficient tear production in the absence of an autoimmune disease. This classification of dry eye is predominantly a result of age-related dry eye, in which the function of the lacrimal gland is dissipated by old age. Less common forms of Non-Sjögren Syndrome Dry Eye are a result of systemic drug use, reflex hyposecretion resulting from sensory or motor block, and scarring over wounds on the conjunctiva, the membrane that lines the eyelids 2. All of the former conditions result in disruption of lacrimal gland production, and produce symptoms of ADDE. The second major classification of dry eye, Evaporative Dry Eye (EDE), is the onset of dry eye symptoms due to abnormal evaporation of water from the exposed ocular surface 2. EDE5 can be further divided into two subclasses. The first, intrinsic EDE, is the obstruction of the regulatory system of evaporation. This includes Meibomian Gland Disease, meager lid congruity and dynamics, low blink rate, and the use of systematic retinoids 2. Extrinsic EDE, the second subclass, is a result of pathological effects on the ocular surface that increase evaporation. Included in this subclass are contact lens wear, ocular surface diseases, and vitamin
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