Biochemical and Biomedical Engineering Research Group
Group Director: Professor Julian Chaudhuri, Tel: +44 (0) 1225 386349
The explosion of biological research and discovery is giving rise to a new generation of biologically based products and processes that can be used in biotechnology and medicine. In order to make full use of this new biology, it is crucial that biochemical and biomedical engineers translate the basic science into practical technology that can be widely used. The Biochemical and Biomedical Engineering research group has a wide range of interests that involve interdisciplinary research that is at the interface between biology, chemistry and chemical engineering.
Tissue Engineering
The Department leads a multi-disciplinary research group that is developing methods of growing human cells and tissues outside the body in order to repair or replace damaged tissues. Following implantation, the new tissues should become integrated into the human body and carry out their natural function. Our research is focused on the regeneration of cartilage, bone and blood vessels, through cultivating the composite cells on both natural and synthetic polymers.
The reconstitution of complex three-dimensional tissue structures is carried out in purpose-designed bioreactor systems. The bioreactor environment allows for careful control of the environmental conditions to optimise the growth of each cell type and its position in the overall structure. Controlling the growth and proliferation of the cells should lead to enhanced tissue properties, and thus deliver the required performance when integrated into the surrounding tissue.
Smart Biomaterials
Self-assembling biological structures and polymers that can respond to their environment provide a wide range of interesting opportunities. We are working on the development of "smart" biological membranes that can interact with their environment. These may be used as coatings for therapeutic agents which can be inserted into the body, and can release a drug or other active agent in response to the state of the patient: for example, by monitoring blood sugar levels and releasing a controlled flow of insulin in response. A second use for these materials is as self-repairing biocompatible surfaces for coating replacement joints, other prosthetics and medical devices used in invasive treatments. Smart polymer systems may also be used as fabrics for the production of clothing that responds to the state of the person wearing it. This has applications in sport, medicine and survival in extreme environments.
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Schematic of composite hydrogel (bold lines denote covalent links):
A - Gel porosity is reduced by affinity crosslinks that exclude large molecules, eg insulin (large blue dot)
B - Glucose (small red dot) diffuses in and competitively displaces affinity crosslinks.
C - Insulin is able to diffuse into the more highly porous gel
D - Insulin diffuses through the gel providing the concentration gradient and glucose concentration is maintained.
Pharmaceutical technologies
The Department is exploring the application of supercritical fluids to produce defined coatings on pharmaceutical products. The aim is to produce a "clean technology" process that could replace existing processes in the pharmaceutical industries that currently use solvents, both chlorinated and non-chlorinated, which are harmful to the environment.
The recovery of the products of fermentation and biotransformation processes is being explored in a number of application areas. Functionalised fluid polymers based on inorganic polymers are being developed and assessed for use as supported liquid membranes for selective separation and extraction. Affinity interactions, based on a ligand tentacle approach, are being exploited to develop an alternative to conventional chromatography resins. The work covers two aspects of design and development: synthesis and characterisation of polymer supported ligands, and synthesis of tentacle resins. We have extended this research into the separation of different cell types. These include separation of malignant from healthy cells, isolation of specific mutants during strain development, and selective removal of contaminants during extended fermentor operation.
Producing therapeutic quantities of substances such as human growth hormone and insulin can be time-consuming and expensive because recombinant micro-organisms generally produce proteins which are inactive. Activity can be regained through a series of steps known as protein refolding, but it is a slow and low-yielding process. We have recently explored the use of mathematical models to optimise refolding reactor operation, reversed micelles, use of the chaperones for in vitro refolding, and the use of hollow-fibre ultrafiltration membranes to minimise protein aggregation. The use of gel filtration matrices to carry out refolding has proved particularly successful. This technique allows the protein to be refolded at high concentration, minimises aggregation and purifies the product in a single operation.
Extremophile Biotechnology
Organisms have evolved to live in almost every environment on Earth, even the most extreme, such as hot sulphur springs, volcanic vents and the salt-laden Dead Sea. These extremophiles open up new opportunities for the exploitation of living organisms and their components to create industrial products and processes, with the clear advantage of clean, efficient and safe technology. Most enzymes from mesophilic (or "conventional") organisms will denature and lose their biological activity above 45°C, at pH values outside the range 5 to 8, or in non-aqueous solvents. Extremophiles, which are generally micro-organisms, have adapted to live outside these confines. The cells and their constituents are extremely stable, and offer considerable biotechnological potential.
We are also exploring the potential for using extremophile organisms in the treatment of industrial effluents. Many effluents resulting from the synthesis of industrial chemicals are not treatable by conventional biological methods, and they are currently treated using expensive and environmentally questionable technologies such as incineration. The ability of extremophile organisms to survive in "difficult" environments could be exploited to develop new biological solutions for these problems. We are working on techniques for the hybridisation of organisms to give them the ability to handle wastes containing mixtures of compounds that in combination pose particular challenges. We are also developing novel membrane bioreactors for accelerated culture evolution.
Academic Staff
Dr Tom Arnot: extremophile organisms, membrane bioreactors, water and waste water treatment and recycling, membranes, emulsion processing (particularly nano-emulsions and particles) and bioproduct recovery, bioprocess control and modelling.
Dr Mike Bird: study of interactions between surfaces and bioproducts in pressure driven synthetic membrane systems; deposition and removal of whey proteins and starches from heat exchange surfaces.
Dr Julian Chaudhuri: development of bioreactor systems for tissue engineering; regeneration of bone, cartilage, ligament tissue; formation of small diameter vascular grafts; expansion and differentiation of mesenchymal stem cells.
Dr Marianne Ellis: development of constructs to aid the regeneration of damaged human organs using tissue engineering principles; the work combines chemical engineering techniques with cell biology, pharmacology and materials science.
Dr Richard England: membrane separations of gases, vapours and liquids, and on the production and highly selective separation of compounds of pharmaceutical interest. A recent development is the application of supercritical fluids to produce defined coatings.
Dr John Hubble: bioaffinity interactions between cells and surfaces; lectin-based affinity chromatography techniques for fractionation of oligosaccharides; development of smart membranes for controlled solute delivery.
Dr Tim Mays: low-cost monolithic carbon adsorbents from bamboo and other canes; thermal stability of olive stones, forest residues and other biomass used in co-combustion with coal in energy conversion systems.
Dr Semali Perera: novel membranes for industrial separations and medical applications; development of novel blood oxygenators; hollow fibre membranes for recovery of anaesthetic gas and carbon dioxide removal from breathing air.
Dr Pawel Plucinski: application of structured fluids (microemulsions) for separation (micellar enhanced ultrafiltration, cloud-point separation, micelles as carriers for extraction and liquid membranes) and reactions (immobilisation of catalyst and/or reactant in a micellar phase).
Dr Sean Rigby: Micro-focus X-ray (MFX) imaging and NMR studies of controlled drug release; mathematical models of controlled drug release.
Links
Centre for Regenerative Medicine (http://www.bath.ac.uk/crm/)
Centre for Extremophile Research (http://www.bath.ac.uk/cer/)