Improving Biocompatibility of Implantable Bioelectronics using Zwitterionic Cysteine
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Recent advances in bioelectronics have allowed for faster diagnoses of diseases as well as treatments for disorders that were previously considered incurable. The performance of these devices is, however, severely hindered in-vivo due to the body’s inherent immune response. Surface fouling, rapid oxidation, and fibrous encapsulation are some of the common issues that reduce device performance and lead to device failure. Overcoming these issues becomes especially critical when a bioelectronic is designed for prolonged exposure to the host in the form of an implant. Constant exposure to the host results in rapid deterioration of device functionality and a secondary surgery is often required to replace the dysfunctional device. The inclusion of various surface modifications, specifically zwitterionic coatings, have recently demonstrated promising results in prolonging a device’s performance in-vivo. An extensive literature review indicates that current antifouling coatings are mainly composed of long chain hydrophilic or zwitterionic polymers; however, these thick polymer brushes are often undesirable for bioelectronics, especially devices designed for electrotherapy as the therapeutic electric pulse decays exponentially with respect to coating thickness. There is a growing need for an engineered surface that is biocompatible, resistant to nonspecific protein adsorption, and does not interfere with the device function in order to prolong the bioelectronics’ in-vivo lifetime. This research focuses on developing an ultra-thin and highly zwitterionic antifouling coating that is also biocompatible and versatile. Cysteine is selected as the coating material because it is a small biomolecule, highly zwitterionic at physiological pH, inherently biocompatible, and practical to fabricate. By optimizing the fabrication process, a monolayer cysteine coating of 8.64Å in thickness is achieved. X-ray photoelectron spectroscopy confirms the protonation of the amine group and the deprotonation of the carboxyl group, and that 87.84% of the surface cysteine is zwitterionic when fabricated at room temperature. This zwitterionic percentage is increased to 94.47% by increasing the reaction temperature to 330K. The adsorption kinetics of zwitterionic cysteine onto a gold surface is studied through monitoring a liquid interface quartz-crystal microbalance in real time and the rate constants are calculated. Cysteine is also inherently biocompatible because it is an amino acid that exists in, and is produced by, our body. Fabrication of a cysteine monolayer is also practical; the sulfur headgroup on cysteine allows for a one-step synthesis onto a gold substrate without the need of a linker molecule. The fabrication can be completed in solution, which allows for the coating of curved or ridged surfaces that can be challenging for other coating processes such a vacuum deposition. Investigation towards the antifouling performance of zwitterionic cysteine begins by quantifying the hydration layer around the molecule. Surface hydration is a key attribute that dictates a material’s antifouling performance. The layer of water associated with the surface acts as an energy barrier that proteins must overcome in order to adsorb onto the surface. Molecular dynamic simulations indicate that a zwitterionic cysteine molecule associates 43.89 water molecules per nm3, which is comparable to established zwitterionic coatings. The degree of surface fouling from various plasma proteins and human blood was quantified by a liquid interface quartz crystal microbalance in real time, and a zwitterionic cysteine surface can reduce fouling from BSA by 95%, fibrinogen by 93%, and human blood by 93% compared with an untreated gold surface. This thesis demonstrates that an ultra-thin monolayer of highly zwitterionic cysteine capable of significantly reducing biological fouling can be fabricated through solution chemistry. This technology exemplifies the tremendous potential of engineering at a nanoscopic level and has application in the field of bioelectronics, tissue engineering, contact lenses, marine membranes, and drug delivery.
Cite this work
Peter Lin (2017). Improving Biocompatibility of Implantable Bioelectronics using Zwitterionic Cysteine. UWSpace. http://hdl.handle.net/10012/11762