Nanostructured model implants for in vivo studies: influence of well-defined nanotopography on de novo bone formation on titanium implants

An implantable model system was developed to investigate the effects of nanoscale surface properties on the osseointegration of titanium implants in rat tibia. Topographical nanostructures with a well-defined shape (semispherical protrusions) and variable size (60 nm, 120 nm and 220 nm) were produced by colloidal lithography on the machined implants. Furthermore, the implants were sputter-coated with titanium to ensure a uniform surface chemical composition. The histological evaluation of bone around the implants at 7 days and 28 days after implantation was performed on the ground sections using optical and scanning electron microscopy. Differences between groups were found mainly in the new bone formation process in the endosteal and marrow bone compartments after 28 days of implantation. Implant surfaces with 60 nm features demonstrated significantly higher bone-implant contact (BIC, 76%) compared with the 120 nm (45%) and control (57%) surfaces. This effect was correlated to the higher density and curvature of the 60 nm protrusions. Within the developed model system, nanoscale protrusions could be applied and systematically varied in size in the presence of microscale background roughness on complex screw-shaped implants. Moreover, the model can be adapted for the systematic variation of surface nanofeature density and chemistry, which opens up new possibilities for in vivo studies of various nanoscale surface-bone interactions

Standardisation of magnetic nanoparticles in liquid suspension

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way—standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way

Functionalized Biomaterial Surfaces by Micro- and Nanofabrication

In the field of biomaterials, well-defined nano- and micropatterns or features at material surfaces can serve both as models for investigating material-biosystem interactions and as functional features for inducing, hindering or measuring specific bioreactions or biologic responses. Important bioreactions include protein adsorption and conformation, cell attachment and function, and adhesion and function of organized tissues or whole organisms. In this thesis, several studies are presented where the following functionalized materials have been micro- or nanopatterned and evaluated in biological systems: (1) Silicon substrates with patterned silver nanoparticles for probing biomolecule detection via SERS; (2) titania ceramic substrates with micro-cavities for culturing liver cells in vitro with preserved phenotype; (3) elastic silicone coatings with micro-pyramids and riblets to prevent marine biofouling by barnacle attachment; (4) silicon and epoxy model porous substrates containing interconnecting microchannels to investigate cell attachment and spreading as a function of substrate porosity; (5) silicon substrates with standing cantilevers for investigation of mechanical cell-substrate interactions. In all these studies, the main task was to achieve a well-controlled and systematic variation of the most relevant surface microscopic characteristics (chemical, topographical or mechanical), in order to tune or optimize the surfaces for their best functional performance, or to gain phenomenological understanding of how microscopic surface properties influence physical or biological interactions at surfaces. Electron beam lithography, photolithography and micro-replication techniques (such as injection molding, embossing and casting) were used to pattern biological test substrates on nanometer and micrometer length scales. Geometrical parameters and surface morphology of microfabricated surfaces were evaluated by scanning electron microscopy and stylus profilometry. Several surface sensitive techniques (x-ray photoelectron spectroscopy, Auger electron spectroscopy, secondary ion mass spectroscopy, contact angle measurements) were used to characterize chemical composition and wettability of the surfaces. Micromechanical characteristics of fabricated flexible structures were probed using atomic force microscopy in "force calibration" mode. It is demonstrated that the lithographic and replication methods used are excellent tools for preparing well-controlled micro- and nanopatterned surfaces in several materials. By systematically varying parameters of such patterns, mechanisms involved in such diverse areas as surface enhanced Raman scattering and marine biofouling have been proposed or verified. In addition, these patterning methods offer the possibility to design cell culture substrates that enhance the preservation of cell phenotype, or, alternatively, intentionally modify their behavior. The latter led to the discovery and development of a new way to measure and map the lateral forces exerted by cells on material surfaces in vitro

Functionalized Biomaterial Surfaces by Micro- and Nanofabrication

In the field of biomaterials, well-defined nano- and micropatterns or features at material surfaces can serve both as models for investigating material-biosystem interactions and as functional features for inducing, hindering or measuring specific bioreactions or biologic responses. Important bioreactions include protein adsorption and conformation, cell attachment and function, and adhesion and function of organized tissues or whole organisms. In this thesis, several studies are presented where the following functionalized materials have been micro- or nanopatterned and evaluated in biological systems: (1) Silicon substrates with patterned silver nanoparticles for probing biomolecule detection via SERS; (2) titania ceramic substrates with micro-cavities for culturing liver cells in vitro with preserved phenotype; (3) elastic silicone coatings with micro-pyramids and riblets to prevent marine biofouling by barnacle attachment; (4) silicon and epoxy model porous substrates containing interconnecting microchannels to investigate cell attachment and spreading as a function of substrate porosity; (5) silicon substrates with standing cantilevers for investigation of mechanical cell-substrate interactions. In all these studies, the main task was to achieve a well-controlled and systematic variation of the most relevant surface microscopic characteristics (chemical, topographical or mechanical), in order to tune or optimize the surfaces for their best functional performance, or to gain phenomenological understanding of how microscopic surface properties influence physical or biological interactions at surfaces. Electron beam lithography, photolithography and micro-replication techniques (such as injection molding, embossing and casting) were used to pattern biological test substrates on nanometer and micrometer length scales. Geometrical parameters and surface morphology of microfabricated surfaces were evaluated by scanning electron microscopy and stylus profilometry. Several surface sensitive techniques (x-ray photoelectron spectroscopy, Auger electron spectroscopy, secondary ion mass spectroscopy, contact angle measurements) were used to characterize chemical composition and wettability of the surfaces. Micromechanical characteristics of fabricated flexible structures were probed using atomic force microscopy in "force calibration" mode. It is demonstrated that the lithographic and replication methods used are excellent tools for preparing well-controlled micro- and nanopatterned surfaces in several materials. By systematically varying parameters of such patterns, mechanisms involved in such diverse areas as surface enhanced Raman scattering and marine biofouling have been proposed or verified. In addition, these patterning methods offer the possibility to design cell culture substrates that enhance the preservation of cell phenotype, or, alternatively, intentionally modify their behavior. The latter led to the discovery and development of a new way to measure and map the lateral forces exerted by cells on material surfaces in vitro