Engineering Man (2)

20/03/2006

Kidneys. Livers. Hearts. Scientists might soon be able to grow any organ you need. Duncan McMillan takes a look into regenerative medicine.

The Royal School of Mines is all about the science of the very big and the very permanent. But tucked behind its austere fašade on Prince Consort Road is a team dedicated to the study of the tiny and the impossibly fragile. They are, helping to put Imperial College at the cutting edge of tissue engineering, a field that promises everything from sophisticated tissue repair to DIY organs and 'soft' cybernetic implants.

Led by Dr. Molly Stevens, the team is a diverse one, including surgeons, computer scientists, cell biologists and engineers. Much of this expertise is focussed on manipulating microscopic artificial environments in order to cultivate and control different types of cell. Basically, if you can understand what external processes control the activity of cells you can replicate those to your own advantage. As Stevens says: "If we can discover what the correct intricate melange of cues is and engineer materials to present these cues then we may be able to make much more intelligent materials for tissue regeneration."

That "intricate melange" means that tissue engineering isn't simply a matter of making a kidney-shaped mould, pouring in a bunch of stem cells and waiting for a functioning organ to appear. Researchers are finding that a much more subtle design is necessary, a design with a scale in the region of millionths and billionths of a metre.

Stevens and team member Julian George published a review paper in Science last year that outlined the challenges of engineering environments for growing tissue cells. Much of the latest research is aimed at mimicking the properties of an exquisitely fine structure within tissues called the Extra Cellular Matrix, or ECM. The ECM provides support for cells – cells that aren't 'anchored' to the ECM become free agents. Such cells commit suicide, so the ECM is crucial to maintaining the health of the tissues in an organ, but its role goes much further than simply giving cells something to hold onto. This environment helps coordinate everything from cell movement in developing embryos to organ growth and wound repair. The structure and chemical composition of the ECM can help determine the internal composition of cells – even which genes they express. Bioengineers have realised that if you can create an artificial scaffolding to copy the properties of structures in living organs, you can have far greater control over the cells you put inside that scaffolding.

So, how do you build an artificial scaffold with struts many times narrower than the cells they hold? One approach being developed is electrospinning. Electrospinners create incredibly fine artificial threads by injecting a polymer jet across an electric field of around fifty thousand volts. Stevens' team recently finished building one of their own in a setup whose Heath Robinson appearance belies its careful design. They have begun working with the polymer PMMA, better known as Perspex, and are now moving on to try biodegradable polymers, such as collagen and peptide-polymer hybrid systems.

When I went to see the electrospinner in action, I half-expected arcing blue electricity and great tumbleweeds of plastic. The reality is somewhat more modest, but no less fascinating; as the electrospinner warms up gossamer-thin threads begin to stream down from the nozzle at the top, to a wire frame on the base of the box. After a quarter of an hour, the collector resembles a spider's jungle gym, covered in whispery filaments measuring in the nanometre range up to 10 micrometres in diameter.

The end product is all very pretty, but what's the point? According to Stevens, they: "plan to use it to make highly controlled bioactive nanofibres that we can pattern into 3D scaffolds to support cell growth." Making those fibres bioactive will involve adding to the polymer mix proteins, like fibronectin and laminin, giving the cells something to bind to. Later investigations will try to tease out the roles of the many other proteins in what Julian George calls the "symphony of interaction" between cells and the ECM. As he says, they can hope to find out "what effect each piece has on cells by re-inserting them into our synthetic matrices....just, there's quite a few pieces to choose from!"

What next with all this? Regenerative medicine will be one of the primary applications of the work being done by Stevens' group. According to a 2004 report the medical uses for tissue engineering range from replacement heart valves and corneas to neurological repair and even transplantation of whole new organs. Stevens suggests that, in time, people will have tissue-engineered organs and enhancements grown from their own stem cells. Researchers at Kings College, London have already worked out how to use adult stem cells to recreate whole new teeth.

The Science paper ends by describing a variety of potential future applications. These include biosensors, implanted directly into the body, which could be used for detecting specific substances or pathogens. Using tailor-made structures, so-called 'cybernetic' components would be partially or completely derived from living tissue, rather than simply being implanted "spare parts". Whether such enhancements are desirable, or even practicable, is open to debate, but it's certain that we have only just begun to investigate the possibilities of tissue engineering and that Imperial College is at the forefront of those investigations.

© FELIX 2008
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"Researchers have worked out how to use adult stem cells to recreate whole new teeth."