Health
The development of new materials and processes is essential for today's health care. The requirements in these areas are very diverse, be it biocompatibility, degradability or stability, and offer a challenge for the scientists involved in their development.
Implants are used on a regular basis in bone fracture, as permanent joint replacements or in dentistry. Scaffolds provide a basis for tissue engineering or even the growth of artificial organs. The capsules of drugs are designed to release a compound at a certain time or with a certain rate.
In order to develop such materials, a profound understanding of their natural counterparts is essential. Scientists thus study the structure, the functionalities and the mechanisms that nature itself offers, such as the hierarchical structure of bone, lubrication mechanisms in joints or bacterial or cellular adhesion mechanisms. These findings may provide the basis for the design of intelligent materials.
However, the role of materials in health care is even broader. Many of the screening mechanisms in medicine, be it for the detection of diseases or the development of new drugs, rely on materials developments. In these fields it may be the structuring and processing of materials, which is essential for the sensitivity and reliability of the devices.
Research groups that develop and study materials and processes for health work at the interface of materials science, engineering, biology, chemistry, physics and medicine. Please find below a list of projects in the following fields:
Biomaterials
This project involves the design of new magnesium alloys for biodegradable implants with applications in vascular intervention and osteosynthesis. The overall performance of the Mg–Y–Zn alloys developed in this context is considered promising for degradable stent applications and underlines the efficiency of the design approach. The new alloys exhibit high room-temperature ductility at sufficient strength, reveal slow and homogeneous degradation behaviour, and induce an adequate biological response.
Peripheral nerve injuries are frequent, causing substantial work leave, chronic disabling and healthcare expenses. Microsurgical repair is the current treatment of choice. However, the clinical outcome is often disappointing, because of axonal misrouting and the long time required for regeneration. In this project, we develop biodegradable nerve conduits that are loaded with glial cell-derived neurotrophic factor and/or nerve growth factor. The aim of this work is to increase significantly the speed of axonal regeneration and quality of target re-innervation in terms of function. This medical bioengineering project is conducted in close collaboration with plastic surgeons and molecular biologists.
Some surface-anchored polymer brushes show a temperature-sensitive swelling behaviour, which can be exploited in the harvesting of cell sheets for tissue engineering. This study provides a first theoretical framework for relating the multiple involved parameters to the swelling properties of the brush. The adsorption of proteins and the behaviour of a Poly(N-isopropylacrylamide) (PNIPAM) brush are modeled in terms of the involved changes in free energy and compared with experimental evidence. The results of this study allow predicting the effect of tuning parameters such as polymer surface density and polymerization degree, which may facilitate improving the utility of such thermoresponsive brushes.
Bone repair and regeneration of defects with bioresorbable implant materials are in great demand in reconstructive surgery. We showed that amorphous tricalcium phosphate nanoparticles synthesized by a flame spray process can be applied as bone cement. The use of nanoparticles enables the formation of smoothly injectable cements that closely resemble the structure of human bone. Flame spray synthesis can also be used to synthesize complex bioactive glass nanoparticles. Preclinical in–vivo tests are currently being run in collaboration with the University Hospital in Zurich, with the aim of elaborating new applications for these materials.
Functional Materials and Devices
Encapsulation is essential in areas ranging from food sciences to pharmaceuticals, cosmetics and materials science. Capsules prepared with conventional technologies can be used to protect sensitive substances, release chemicals in a delayed manner or physically separate ingredients from the outside environment. The preparation of capsules with further functionalities, capable of responding to external stimuli in a deliberate and reversible fashion is highly desirable in many applications. We study novel approaches to prepare smart, responsive capsules that could be implemented in hybrid structures to create new functional materials.
Hospitals are confronted with poisoned patients on a routine basis, ranging from drug overdose to accidental toxic exposures. Unfortunately, for many life-threatening intoxications, specific antidotes are not available. One possible strategy for the management of overdose consists in administering particulate carriers, which reduce the bioavailable drug concentration in the body. Our laboratory is currently developing long circulating vesicles, which combine all required features for the treatment of overdoses. These novel vesicles may not only be useful for the prevention and/or treatment of drug acute toxicities but could also treat poisoning to other toxins, such as pesticides and chemical weapons.
Bioelectronics is a recent science and includes the close juxtaposition of biologically active molecules, cells, and tissues with conventional electronics. Several CMOS-based microelectrode arrays (MEA) with a high spatial and temporal resolution have been developed at our laboratory during the past years. Cells are grown directly atop these fully processed microelectronics chips. The devices require surface engineering in order to provide biocompatibility and a tight coupling between the surface and the cells. They can be used for multisite extracellular recordings from electrogenic cells, such as neurons, heart cells, or muscle cells, for studying fundamentals of learning processes, of aging and mental diseases, for assessing cellular behavior upon exposure to pharmacological agents or hazardous substances, or for monitoring cell responses to electrical stimulation.
We develop three-dimensional suspension arrays for highly parallelized analysis of engineered microorganisms or evolved enzymes. Single cells harbouring putatively optimized metabolic pathways or enzymes are encapsulated in nanoliter-sized reactors and cultivated into microcolonies. These populations are confined to their nanoliter reactor and can then be analysed in extremely high frequencies based on optical signals (up to 106 analyses/day) or enzyme activities (1010/day).
Polymers have significant potential as functional and structural materials in microsystems technology, because of their broad variety of properties and low cost. Our projects focus on determining and controlling the mechanical and electrical properties of polymer structures at the micro scale. Materials under investigation are thermosetting polymers, e.g. photosensitive SU-8 and PI, thermoplastics such as PMMA and PE, and polymer composites filled with magnetic nanoparticles. These materials can find applications especially in the health care field due to their biocompatible properties.
Biological Materials
This research is concerned with structure-function assessment of bone, and for this reason we investigate 3D approaches for quantitative bioimaging as well as experimental and computational mechanics. Bone fracture as assessed by micro-computed tomography has been combined with micro- compression testing in order to understand fracture at a 3D microscopic scale. With synchrotron radiation-based CT systems, we extend this to the nanometer scale and a cellular analysis of the material. These tools are also used for tissue engineering of bone, where substitute tissues that restore or improve function are developed and monitored, and can serve as models for further development.
Knowledge how cells sense and respond to their native environments is crucial to develop the next generation of soft tissue scaffolds. We are currently focusing on elucidating how extracellular matrix is designed to function as a mechanochemical signal converter that is activated by cellular traction forces. Computational simulations are combined with fluorescence resonance energy transfer (FRET) spectroscopy and surface engineering to investigate how cells stretch and otherwise alter their extracellular matrix in response to environmental conditions, and how this regulates cell signaling and fate.
The mechanical behaviour of human tissues, organs and implants is investigated for applications in medicine: (i) diagnosis (e.g.: detection of liver pathologies; malfunctioning uterine cervix; premature rupture of fetal membrane), (ii) surgery planning (facial tissue models for plastic surgery simulations), (iii) tissue replacement/ implant development (intervertebral disc, supportive implant meshes for hernia or laxity). Our aspiration experiment provides information on the in vivo mechanical behaviour of human tissues. Mechanical data are correlated with histological observations.
In-vivo amyloid fibers from denaturated globular proteins or peptide sequences occurring in living cells are typically associated with neuro-degenerative diseases and disorders. Amyloid fibers can, however, be designed in vitro from food-grade proteins to generate new structures and building blocks with unchallenged properties. We use scattering techniques and single molecule microscopy analysis to unravel the structure and properties of these fibers as a function of processing conditions such as pH, ionic strength, temperature and concentration.
Mechanical loading is an important factor regulating bone mass and shape. An understanding of the mechanisms governing anabolic bone adaptation could ultimately lead to the development of pharmacological agents which mimic this mechano-sensitive response, thereby offering novel strategies for the management of bone diseases such as osteoporosis. To gain an understanding of bone morphology and the associated biochemical pathways, we employ in vivo measurements, biochemical methods and computational modelling to investigate the changes in load induced bone adaptation using transgenic mouse strains.
Bioinspired Materials
A unique feature of hard biological structures such as bone, teeth and seashells is their intimate combination of inorganic and organic matter. Although artificial composites have long been developed and applied, man-devised technologies are still not capable of producing hybrid materials with the intricate structural design found in hard biological materials. We investigate new processing strategies for the fabrication of hybrid materials exhibiting bioinspired structural features and new, unusual properties.