Ian Wark Research Institute
ARC Special Research Centre
ARC Special Research Centre
Research Area: Bio-interfaces, biomaterials, interface science, surface analysis, biocompatible coatings
Degree: Honours
Supervisors: Prof Hans Griesser and
Prof Bill Skinner
Description: This project aims to study and interpret interfacial interactions between the surfaces of solid synthetic materials suitable for biomedical device applications ('biomaterials') and biologically significant lipid molecules. The motivation for this study is that interactions between biomaterials and proteins have been the subject of considerable study, but currently used biomaterials still cause adverse reactions when they come in contact with biological systems. Adverse biological reactions to biomedical devices span the range from being merely inconvenient, such as the fouling of contact lenses and bio-sensors, to life-threatening responses such as the clotting of blood in small diameter artificial blood vessels and the formation of deposits on heart valves. The hypothesis of this study is that the focus on proteins may have neglected to take into account the role that lipids in biological fluids may play in the presence of a synthetic interface. Is the failure of so much research to achieve full compatibility between biomaterials and biological environments due to the neglect of material/lipid interactions? This project thus is targeted at the fundamental science aspects of biomaterials/lipids interactions. The fundamental understanding acquired in this project is expected to provide a basis for the rational design of improved biomedical devices.
Modern biotechnology, health care devices, and bio-diagnostic assay technologies require synthetic polymeric or ceramic materials that need to meet a number of requirements such as strength or flexibility. A key requirement, however, is that the material possesses appropriate surface properties. The reason for this is that biological molecules encounter the surface of biomaterials, and the chemical composition and properties of material surfaces determine the biomedical consequences of the interfacial encounter between biological molecules and the material surface. It is well known in the biomaterials literature that immediately after a material contacts a biological environment �for instance a protein solution in a vial, or blood or soft tissue when an implant is used in human medicine - various proteins reach the surface of the synthetic material and interact with it. Some of the proteins stick irreversibly to the surface; other proteins desorb again. Adsorbed and denatured proteins then cause biological reactions that can have various, usually adverse, biological consequences. In the case of biomedical implants, the irreversible, uncontrolled accumulation of biological material on the surface of devices does not replicate the natural structures and functions at that body site, and typically causes adverse reactions such as fibrous capsule formation adjacent to soft tissue implants or the formation of blood clots inside synthetic vascular grafts.
Researchers have developed coatings that greatly reduce the adsorption of proteins onto synthetic biomaterials, yet clinical evidence is that such coated materials do not eliminate adverse biological reactions in human implant applications. Is this due to lipids? Lipids are an important component of blood, and also of the tear film on eye. Thus, do contact lenses foul and artificial blood vessels clot because lipids interact with the surface or affect protein/biomaterial interactions? And how do different surface composition mediate the effects of lipids? What is the best, minimally interactive synthetic surface?
Aims and Significance: The principal aim of this project is to acquire a fundamental understanding of interfacial interactions between biomaterials and biological lipids, and how the presence of lipids may affect protein/material interactions. It is known that different materials elicit different biological responses, but molecular understanding of the underlying interfacial interactions is lacking. Thus, by understanding such interactions, one may be able to establish design "rules" for optimal biomaterials surfaces for various biomedical applications. Such rationally designed, novel biomaterials are expected to open up a range of biotechnological applications in bio-diagnostics and health care industries.
Such research is necessarily inter-disciplinary, and the student will acquire skills and understanding of materials science, surface science, biochemistry, and biology. This will equip him/her well for future employment in biotechnology areas.
Methodology: In the first stage of the project, a range of materials and coatings will be selected on the basis of current models of interfacial interactions between proteins and materials. These materials will be assayed in established tests for interactions with proteins to establish a base line. The same materials will be subjected to assays, to be developed in this project, that probe interfacial lipid/biomaterial interactions. Of particular relevance will be the use of modern spectroscopic surface analysis techniques such as XPS and ToF-SSIMS that can probe for small amounts of adsorbed lipids on solid surfaces. In the next stage, biomaterials surfaces will be exposed to combined solutions of lipids and proteins, and it will be studied how these molecules compete for available surface adsorption sites. Which molecules adsorb and which ones don't? Do they do so individually, or is there synergy and antagonism, for example perhaps by initially adsorbed lipids affecting protein adsorption? Do protein/lipid complexes formed in solution dissociate in contact with a biomaterial surface? ToF-SSIMS analyses will be crucial as this method can distinguish between proteins and lipids at much below monolayer adsorbed amounts. The direct probing of interfacial forces will be investigated using colloid-probe AFM. These sets of results will then be interpreted in terms of interfacial interactions and the criteria for an optimal biomaterial surface for specific applications. Finally, in collaboration with clinicians it will be tested whether the knowledge gained translates into benefits in real-life applications such as contact lenses.
References
1) BD Ratner, 'New ideas in biomaterials science - a path to
engineered biomaterials', J. Biomed. Mater. Res. 27, 837-850 (1993).
2) JC Vickerman, Ed., Surface Analysis - The Principal Techniques, John Wiley & Sons, Chichester, 1997.
3) P Kingshott, H Thissen and HJ Griesser, Biomaterials 23, 2043-2056, 2002
