| Cellular responses are highly influenced by the surrounding physiological environment through complex interactions with mechanical forces, biochemical stimuli, and structural components of the extracellular matrix (ECM). Due to the impact of the ECM architecture on cellular responses, significant research has been dedicated towards developing biomaterials that mimic the physiological environment for design of improved medical devices. Surface topographies with microscale and nanoscale features have demonstrated an effect on numerous cellular responses; however, determining relationships between biological responses and surface topographies are difficult to establish due to differences in cell types and biomaterial surface properties. Therefore, it is important to optimize implant surface feature characteristics to elicit desirable biological responses for specific applications. The goal of this work was to evaluate the effects of microstructured and nanostructured biomaterials on in vitro biological responses through reproducible fabrication of microscale and nanoscale surface topographies, comprehensive physico-chemical characterization of material surface properties, and systematic evaluation of biological responses for specific biomedical applications. Several methods for reproducible fabrication of uniform microstructured and nanostructured implant coatings with random and patterned surface topographies were investigated. Fabrication processes included physical vapor deposition (PVD), chemical vapor deposition (CVD), atomic layer deposition (ALD), and two-photon polymerization (2PP). PVD and CVD processes were used to fabricate nanocrystalline diamond (NCD), titanium dioxide (TiO2), and tantalum coatings with varying microscale and nanoscale surface topographies. ALD was used to surface modify commercial nanoporous membranes with well-defined pore sizes using ceramic coatings, including TiO2 and zinc oxide (ZnO). 2PP was used to create zirconium oxide-based 3-D tissue engineering scaffolds with precise, patterned structures. Physico-chemical characterization of the fabricated implant surfaces demonstrated a variety of microscale and nanoscale surface topographies with different surface chemistries. The effects of microscale and nanoscale surface topography on biological responses (e.g., protein adsorption, cell adhesion, cell morphology, cell proliferation, cell differentiation, antimicrobial activity, hemocompatibility) were evaluated using various application-specific cell types (e.g., human bone marrow-derived mesenchymal stem cells, vascular endothelial cells, blood cells/platelets, and epithelial cells). Biological responses were surface feature size-dependent for some biomaterials and cells, while other studies demonstrated no effects of surface topography on cellular responses. NCD coatings with small nanoscale surface features promoted improved endothelialization for vascular stent applications. In contrast, nanostructured TiO2 coatings with large surface feature sizes promoted enhanced osteogenic differentiation of mesenchymal stem cells for improved osseointegration of orthopaedic devices. ALD ceramic thin films altered the surface chemistry of nanoporous materials for enhanced biological properties, including antimicrobial activity (ZnO) and bioactivity (TiO2). The fabrication, physico-chemical characterization, and biological evaluation of microstructured and nanostructured implant surfaces described here have contributed to a better understanding of the effects of microscale and nanoscale structures on biological responses for biomedical applications. |
