Lost an ear? No problem, we’ll just print you a new one

3D printing is now well established. Its application to human health is what interests me.

Freddy was caught in a forest fire. Why did he not run away? Well, actually he did, but Freddy cannot run very fast. He is a tortoise, you see, and the fire overwhelmed him and burnt the shell off his back.

Now, though, Freddy is doing just fine. He is padding around, happy in his new shell. The secret? 3D printing. A team from Animal Avengers calculated the dimensions of his missing shell and made a new one using a 3D printer to make a replica.

The same team have also saved Gigi. Gigi is a Brazilian parrot, found with a severely deformed beak. Again an image of the correct beak was created on a computer and a 3D printer then copied this into a new titanium beak, ideal for opening seeds and cracking nuts.

Most recently Animal Avengers have made a new tooth for a labrador puppy – further evidence of the promise of 3D printing.

I have described biotechnology as the engineering of life. We are already extremely good at engineering stuff that is dead, or was never alive in the first place – metal, stone, plastic and wood. In this sphere 3D printing is now well established.

Daimler are printing plastic spare parts for Mercedes trucks; Thales has printed metal parts for satellites; Airbus has made an ultra light weight motor cycle through 3D printing of aluminium alloys – here is what is looks like:

3D printing has been used to make drones, to make prosthetic arms for dolls, to create artificial coral reefs and even a dress. The technique has obvious advantages. Pieces can be made to order – Daimler, for example, will no longer have to keep a stock of spare truck parts but can make them one by one. And they can be made anywhere there is a 3D printer, saving the cost and time of transportation. Printing allows the creation of shapes that cannot be made by conventional fabrication and the metallic inks and powders give novel qualities such as light weight.

The 3D printing of body parts

It is the application of 3D printing to human health that interests me. Last week ROCHE’s Pharmaceutical Research and Early Development unit reported that it has tested drugs on 3D bioprinted human liver tissue produced by Organovo (AMEX: ONVO), a San Diego company that is a leader in this field. Roche was able to test the toxicity of two compounds, and by doing so on human tissue rather than on animal (mice) models it hopes to gather results that are more accurate in the human context.

Testing of drugs in this way could become the first widespread use of 3D printed tissue. But the ultimate hope is to produce replacement body parts.

This presents many difficulties. Gathering cells is the easy part. If these come from the patient and are then multiplied in the laboratory there should be no problem with immune rejection. But cells do not necessarily want to stack up into three dimensional structures. They need an attractive structure if they are to hang together. This is called a scaffold, and it must either be accepted into the body or else programmed to decompose.

A team from Bristol University has recently reported some progress, by creating a bio-ink made from stem cells, a natural polymer extracted from seaweed and a sacrificial synthetic polymer. Dr Adam Perriman explains the problems:

‘You need a material that is printable, strong enough to maintain its shape when immersed in nutrients, and that is not harmful to cells….When the cell nutrients were introduced, the synthetic polymer was completely expelled from the 3D structure, leaving only the stem cells and the natural seaweed polymer. This created microscopic pores in the structure, which provided effective nutrient access for the stem cells.’

By inducing these stem cells to become cells that secrete bone (osteoblasts) and cartilage (chondrocytes) this printed material can be made into implantable bones and cartilage. Already this type of body part is being created using 3D printing. According to Wohlers Associates the market for printed body parts was worth $537m last year but this is largely derived from titanium replacement hip joints.

At the Inside 3D Printing Conference in New York in April researchers from Johns Hopkins and Princeton unveiled an ear, made by printing a hydrogel with cells and silver nanoparticles to form an antenna.
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The end of donors?

These replacement hip joints and ears are impressive but they are relatively simple. They do not require a blood supply and if they malfunction the patient will not die.

Far more challenging is to print organs that depend upon a blood supply, have multiple different cell types that divide and die, and must be integrated with other organs of the body and the nervous system.

If we could produce ‘living tissue’ that functions properly we could create organs at will and beat the shortage of donor livers, kidney and, most challenging of all, hearts. For now the early targets are small items like skin patches and blood vessels but a recent breakthrough made at the Wake Forest Institute for Regenerative Medicine indicates what might one day be possible.

Its Integrated Tissue and Organ Printing System deposits both bio-degradable, plastic-like materials to form the tissue shape and water-based gels that contain the cells.

With this, researchers printed a lattice of micro-channels, allowing nutrients and oxygen from the body to diffuse into the structures, keeping them alive while they developed a system of blood vessels. In studies a baby-sized ear structure survived and showed signs of vascularisation at one and two months after implantation into a mouse. In another experiment printed muscle tissue was implanted into rats. After two weeks, tests confirmed that the muscle was robust enough to maintain its structural characteristics, become vascularised and induce nerve formation.

Biological engineering has one advantage. Get a pile of bricks and they do not magically come together to form a house. But for reasons that we do not understand cells seem to know what to do. Put stem cells into the brain and they turn into neurons (brain cells).

And functional cells also have the capacity for self assembly – leave kidney cells to their own devices and they will start to form kidney tissue. So while these are early days for regenerative medicine the day when we can safely replace defunct body parts is certainly getting nearer.

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