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Consequences of protein adsorption on bioactive coatings

Research Area: Biomaterials, interface science, surface analysis, bio-interfaces, biocompatible coatings

Degree: Honours

Supervisor: Prof Hans Griesser

Description: This project aims to investigate the reasons why bioactive coatings can rapidly lose their effectiveness when placed in biological environments. Bioactive coatings can have a variety of chemical compositions, and the common denominator is that they have a predictable, known function and thus exert a specific response in the biological environment when a synthetic material is placed in contact with biological environments. Applications for bioactive coatings comprise the control of wound healing around biomedical devices and the mitigation of bacterial infections on implants, catheters and contact lenses. The coatings can consist of hydroxyapatite (for orthopaedic applications), synthetic or natural antimicrobial substances (to combat bacterial colonization), or surface-adsorbed or covalently immobilized protein layers. There has been considerable research into the fabrication and clinical evaluation of such bioactive coatings, but their effectiveness often decreases markedly with time over periods much shorter than is clinically desirable. Thus, it is highly desirable to develop bioactive coatings with longer effectiveness. To do so in a rational fashion, one must understand the reasons for the current limitations. 

One possibility is that when used on biomedical implants, such coatings are attacked by the host body's defense system, which reacts to the trauma caused by the surgical procedure by an inflammatory and wound healing response. At the microscopic level, this comprises attack by proteolytic and oxidative enzymes as well as cells that attempt to engulf the implant (phagocytosis). Thus, it is conceivable that protein-containing bioactive coatings are digested too rapidly by the wound response system. It is, however, less clear why synthetic molecules and coatings should be digested rapidly. Thus, another mechanism may apply : protein adsorption covers the bioactive layer with a random, uncontrolled layer of biological molecules. This adsorbed layer is not capable of exerting the specific bio-responses that one wishes to dictate to the wound healing process. 

Hence, the hypothesis of prime interest in this project is whether uncontrolled, non-specific adsorption of various proteins onto bioactive coating is a major cause of loss of bio-specific responses to such coatings. A second line of investigation is, for protein-based bioactive coatings, whether proteolytic digestion is important. A further question focuses on the role and importance of oxidative enzymes, which conceivably could also attack synthetic bioactive coatings, such as comprising bacterial inhibitors. 

Finally, based on the results from those experimental approaches, designs will be established for bioactive coatings that may provide longer effective times in biomedical implant applications. Such coatings will be tested in collaboration with microbiologists. 

Aims and Significance: The principal aims of this project are to acquire a fundamental understanding of the factors that limit the clinical usefulness and effectiveness of current bioactive coatings. Based on investigation of several possible degradation mechanisms, an understanding will be achieved of the key factors involved for several types of coatings. This will then enable the rational design of strategies for improving the longevity of bioactive coatings. It is expected that the mechanisms may vary for different types of coatings, and hence the paths to improvement may also be different for different types of coatings. This knowledge will underpin the rational design of novel implant surfaces that elicit optimal bio-interface responses. By understanding interactions between bioactive coatings and the host biological environment, one may be able to establish design "rules" for optimal bioactive coatings for various human medicine applications. 

Such research is necessarily inter-disciplinary, and the student will acquire skills and understanding of bio-interface science, gas plasma techniques, coatings and surface science, surface analysis, and protein biochemistry. This will equip him/her well for future employment in materials/biotechnology fields. 

Methodology: Due to the difficulties and cost associated with obtaining reliable clinical data, most experiments will be done in vitro, with a clinical trial only at the final stage for a promising approach. In vitro test systems for studying interactions between materials and biological media/environments are reliable and repeatable. However, to allow testing of hypotheses, they must be designed with care based on a good knowledge of possible molecular biological phenomena. Thus, model test systems will be designed and implemented to probe for proteolytic and oxidative attack on coatings, and for coverage of the bioactive coating by adsorbing biomolecules. Analysis of the effects of these media on the bioactive coatings will be done primarily by surface analytical techniques, particularly XPS and also some SIMS and ellipsometric measurements. Biochemical assays, particularly ELISA, will also be used to probe for biological activity of epitopes. Once the mechanisms are understood and design criteria established for surfaces that can exert longer-term predictable, controlled bio-interface interactions, such coatings will be fabricated and tested first in model systems and finally in a specific application. 

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.

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