Novel micro- and nano-technological approaches for improving the performance of implantable biomedical devices

Abstract

Biomaterials are used in a wide variety of in vivo applications, ranging from joint and dental implants to neural prostheses. The ultimate success or failure of implants mainly depends on the biological interactions (molecular, cellular, tissue) at the implant/tissue interface. Recent advances in micro- and nanotechnology offer a great opportunity to develop intelligent biomaterials and the next generation of implantable devices may well be of achieving the desired tissue-implant interaction and resolving various biomedical problems. The main aim of this thesis work was to design, fabricate and evaluate a novel flexible microelectrode array suitable for use in sub- or epidural electroencephalographic recordings. Other aims were to investigate the opportunities to improve the electrochemical and biological properties of neural interfaces using modern micro- and nanotechnology tools as well as to test whether the micropatterning of thin films can be used to guide the cellular response on biomaterial surface. The developed microelectrode array was implemented on polyimide with platinum which achieved both mechanical flexibility and high quality electrochemical characteristics as demonstrated via impedance spectroscopy. Somatosensory and auditory evoked potentials were successfully recorded with epidurally implanted array in rats with excellent signal stability over two weeks. Subsequently, the signal levels declined, most probably due to the thickening of dura and the growth of scar tissue around the electrodes. It was hypothesized that one obvious reason for this limited life-span was the poor biocompatibility of photosensitive polyimide used as an insulation material in these arrays. However, this possibility was excluded by in vitro cytotoxicity studies according to ISO 10993-5 standard. Furthermore, ultra-short pulsed laser deposition was demonstrated to be an effective method to produce nanotextured platinum surfaces as well as ultrasmooth insulators for further development of neural interfaces. Experiments with osteoblast-like cells and mesenchymal stem cells on micropatterned biomaterial surfaces indicated that even partial coating of silicon with a biocompatible material is an effective way to enhance the cytocompatibility of siliconbased biomedical micro-electromechanical systems. Moreover, it was demonstrated that not only the chemical composition of the materials, but also the shape, edges (height) and size of the features used for surface patterning have a remarkable effect on cell guidance. Overall, the results of the present thesis provide a solid basis for the further development of neural interfaces as well as other types of implantable devices.

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Novel micro- and nano-technological approaches for improving the performance of implantable biomedical devices