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Pathobiology Group

The Pathobiology Group, led by Dr Paul Human, has traditionally focussed on the host response to cardiovascular implants.

Initially, the response to bioprosthetic heart valve constructs fabricated from chemically treated porcine aortic valves or pericardial tissue was studied.  This research concentrated on the phenomenon of dystrophic calcification which is particularly acute in the younger patient and hypothesised and found tantalising evidence implicating a  humoral immune response.

The group now focusses on both humoral and cellular arms of the host immune response to evaluate novel tissue treatments to extend the longevity of bioprosthetic devices through pacification but also remodelling.

Screening of a large number of tissue treatments prepared by the group following in vivo implantation relies on atomic absorption spectrophotometry and histological analysis. This work has provided useful data to the Strait Access Technolgies team prior to large animal testing.

The group also pioneered the use of immunoglobulin fragments to mask immunoglobulin binding on bioprosthetic tissue as a tool for further understanding the implications of a humoral immune response. This relied on standard biochemical techniques including chromatography, electrophoresis and two-dimensional Western blotting.

Restenosis of coronary arteries following balloon injury and deployment of vascular stents has also been shown to result in an antibody response to vascular smooth muscle cells, possibly contributing to intimal hyperplasia. The group has set up a model in mice to evaluate this through the use of knockout strains.

Work involving assessment of the immunogenicity of drug aggregates, specifically an interferon used in cancer treatment, concentrated on the role of mechanical agitation typically experienced in drug delivery pumps. This relied on evaluation of the drug-binding potential of immunoglobulins through enzyme linked immunosorbent assays developed in house as well as the neutralising potential of thereof though cell-based assays.

The group relies heavily on morphology based analysis using histological, immunohistological and electron micrography (gold labelling) techniques. It relies on a variety of in vivo models from subdermal screening models in rats and rabbits to blood circulating models such as sheep and previously primates.