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Hyaluronan hydrogel modified intraocular implants for glaucoma treatment
Glaucoma is a very prevalent eye disease with more than 60 million people affected worldwide. The only form of therapy is the artificial lowering of the intraocular pressure of the aqueous humor, which is the main cause for the disease. This can be achieved for example by the application of an intraocular implant to drain excess liquid. Due to a nonoptimal biocompatibility these intraocular stents often induce inflammation and fibrosis of their surrounding tissue. This subsequently blocks the outflow of liquid through the implant and results in long-term failure of the therapy. The goal of this thesis was the development of a new type of glaucoma implant made from titanium enhanced by hyaluronan hydrogels. The basic concept was the coating of the outer surfaces of a small tube with hydrogels made from hyaluronic acid to enhance cell adhesion for a better biocompatibility and a lower occurrence of inflammation and fibrosis. Simultaneously the interior was to be filled with hyaluronan hydrogels with slightly different properties to block a clogging of the drainage path by cell growth and act as a valve to regulate the intraocular pressure. In addition the economical and work safety aspects for an industrial mass production and biomedical application of these implants were considered. In order to achieve this goal, a number of methods to fabricate, and tools to analyze, hydrogel-enhanced glaucoma implants have been investigated in this thesis. Reaction sequences were developed to simultaneously crosslink and immobilize hyaluronan hydrogels on glass and titanium surfaces by a combination of several established methods. In addition, fluoresceinamine was integrated into the process to generate fluorescently labeled hydrogels, which was an effective tool for further analysis. Also, a number of methods were designed to observe the behavior of the hydrogel-modified implants when exposed to external pressures. It was possible, by using these methods, to verify the stability of the immobilization, with hydrogels within the tubes being able to withstand the pressures encountered in the glaucomatous eye without breaking apart. Furthermore it was shown that a regulation of external liquid pressures by these hydrogel-filled tubes was possible which illustrated these implants’ potential to drain excess intraocular fluid from the glaucomatous eye without causing hypotony. The mechanism of the pressure regulation was further explored and related to the presence of channels within the hydrogels that enabled liquid flow at certain pressure levels. Since the natural occurrence of these channels during the production process of the implants was initially random, two methods were developed to allow their artificial and reproducible creation. This was achieved either by the use of a laser to burn channels into the hydrogels or by the implementation of small glass fibers prior to the gel formation within the tubes. The methods established and the results gained in this thesis provide the means to generate hydrogel-enhanced implants and illustrate their general usability in glaucoma therapy by reducing intraocular pressure. In addition the process for the implant creation was successfully streamlined to allow for a cost effective, low-hazard production on an industrial scale. Future research based on the established concept will comprise the optimization of the hydrogels’ capabilities to either improve or resist cell adhesion as necessary. Also setups will have to be designed for a miniaturization and industrial mass fabrication of the implants.
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540 Chemie
540 Chemistry and allied sciences