Microfabrication for Biological Applications. Preparation, Characterization and Biological Evaluation

Doctoral thesis, 1996

Foreign materials are intentionally placed into patients in the form of medical devices for replacing or repairing damaged portions of the body. Materials also enter the body unintentionally in the form of particulates and fibers, and can then have damaging effects, such as the formation of disease or even cancer. Such is the case for inhaled mineral dusts and asbestos fibers. The interaction between living tissue and a foreign material is, in both cases, governed by the type and state of the host tissue as well as by the physical and chemical properties of the material. Of major importance is the role of material surface properties in reactions occurring at the material-tissue interface. Both the chemical properties and the morphology (i.e., topography, texture, or roughness) of the surface are important. They may act independently or in synergy in producing biological responses to foreign materials. A major goal for future biomaterials research and development is to control biological responses by engineering the surface to carry out specific biological functions. This requires an understanding of the independent roles of chemical versus morphological properties of material surfaces. It is therefore important to be able to systematically and independently vary each of these properties, and to study how they affect biological responses. The latter applies also to materials that unintentionally enter the body. The aim of this thesis work was to develop and apply micro- and nano-fabrication methods to produce well-controlled surfaces and particulates on all biologically relevant size scales. The capabilities of photo- and electron beam lithography to produce systematically and independently varying morphological and chemical features over the size range of nanometers to microns has been demonstrated and critically evaluated. Some of these structures have been used in biological model experiments. The main emphasis has been the development of methodologies to produce, characterize, and apply microfabricated samples for studying cellular interactions. Samples containing spatially patterned, 10 µm square areas of Ti, Al, and V metal films have shown bacterial (S. epidermidis) adhesion preferences for V regions. A second example is the production of free fibers of cross-section 0.1 x 0.5 µm and lengths of 10, 1, or 0.1 µm in gold, titanium, and silicon oxide. The phagocytic response of alveolar macrophages to 10 µm long fibers of titanium and silicon oxide indicate differences owing to differences in fiber material chemistry alone. In addition to these two examples, a variety of structures for potential future biological experiments have been produced. They include 1 - 10 µm features and patterns etched into bulk polymethylmethacrylate or titanium surfaces. The main impact of this work is that it demonstrates the needs and opportunities for microfabrication and nanofabrication in both biomaterials (medical implants and devices, etc.) and respirable fiber research and development. The efforts put forth here therefore form the basis for future applications of micro- and nanofabriaction to biomaterials as well as to various other fields of research.