Monday, March 18, 2013 C7
HEALTH FROM THE EXPERTS DR JONNY ANOMALY life@scmp.com
Germ warfare meets resistance
That
makes
two of us
Bioengineers are using the latest 3-D printing technology to create bones, body parts and, in the future, organs for transplant, writes David Tan
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t was used to create haute couture dresses at January’s Paris Fashion week, Valentine’s Day chocolates in the shape of a person’s face in Japan and, possibly soon – the European Space Agency is toying with this idea – a lunar base on the moon. The sky’s the limit with threedimensional printing, and it’s revolutionising fields from industrial manufacturing to architecture. Medicine has a huge scope for making use of the process. Last week, a man in the US had 75 per cent of his damaged skull replaced with a custom-made implant produced by a 3-D printer. “We see no part of the orthopaedic industry being untouched by this,” says Scott DeFelice, president of Oxford Performance Materials, which made the implant. The implant, approved last month by the US Food and Drug Administration, was made using a high performance polymer that is biomechanically similar to bone. The company plans to create other bones such as femurs, knee caps and hips. Also known as additive manufacturing, 3-D printing is a process of making solid objects from a digital model. An object is created by laying down successive layers of plastic, ceramics, glass or metal. Last month, a team from Cornell University in the US unveiled their artificial ear. The scientists first analysed a digital 3-D image of a human ear, then used a 3-D printer to assemble a mould, into which they injected a mixture of collagen gel from rat tails and cartilage cells from cow ears. The collagen served as a scaffold upon which cartilage could grow, and over three months, the
cartilage grew to replace the collagen. “It takes half a day to design the mould, a day or so to print it, 30 minutes to inject the gel, and we can remove the ear 15 minutes later. We trim the ear and then let it culture for several days in nourishing cell culture media before it is implanted,” says Professor Lawrence Bonassar, leader of the study. The bioengineered ear replacement may be the solution reconstructive surgeons have long wished for to help children born with ear deformities, says co-lead author Dr Jason Spector. Microtia, a congenital deformity where the external ear is not developed, affects thousands of children each year. Many people also lose part or their entire ear in an accident or from cancer. Three-dimensional printing technology is already generating revenue in two areas: dental fabrication of crowns, bridges, and implants; and prosthetics manufacturing. Last month, an 83-year-old Belgian woman, whose chronic bone infection had destroyed her lower jaw, was able to eat and speak again with a 3-D printed prosthetic jaw made from 33 layers of titanium powder that were heated, fused together and then coated with bioceramic artificial bone. The area of “bioprinting” – the 3-D printing of human organs for transplant – however, is still in its infancy. Bioprinters
Lawrence Bonassar of Cornell University shows the ear made by a 3-D printer. Photo: AFP
use a “bio-ink” made of living cell mixtures to build a 3-D structure of cells, layer by layer, to form tissue. This tissue is then developed into organs. In 2011, a team led by Anthony Atala, at the Wake Forest Institute for Regenerative Medicine in the US, revealed the development of a technique to grow engineered urethras for several Mexican boys whose urethras were damaged in car accidents. The scientists took a sample of tissue from the boys and multiplied the cells in the lab before seeding them on a cylinder of biodegradable material. The resultant tube of tissue was transplanted into the boys’ urinary systems. “When they came in, they had a leg bag to drain their urine, and they had to carry it everywhere they went,” says Atala. After the treatment, “these children are now normal”. Replacing human body parts that are primarily made of cartilage, such as joints, the trachea and the nose, is helped by the fact that cartilage does not require a blood supply to survive. Building
Liver tissue, heart tissue, and pancreatic tissue will continue to be central areas for us to explore DR JORDAN MILLER, UNIVERSITY OF PENNSYLVANIA
organs that rely on blood is trickier – though University of Pennsylvania scientists have been making advances in this area. In a study published last year in the journal Nature Materials, the scientists showed that 3-D printed templates of filament networks can be used to rapidly create vasculature and improve the function of engineered living tissues. Without a vascular system, which delivers nutrients while removing waste products, living cells on the inside of a 3-D body part cannot survive. Building a vascular network is tricky because the layer-bylayer fabrication of 3-D printing
LAB REPORT ............................................... Jeanette Wang jeanette.wang@scmp.com Driven to distraction Answering text messages behind the wheel is as dangerous as being twice over the legal alcohol limit, according to a study from various Australian universities and the University of Barcelona in Spain. Twelve healthy volunteers took a driving simulation test to measure their reactions after having consumed alcohol and while using the mobile phone. By comparing the blood/alcohol with the effects of mobile phone usage, they saw that when answering a text message, the level was 1 gram per litre, double Hong Kong’s legal limit (0.5 g/l). A hands-free conversation requiring high cognitive demand measured 0.7 g/l.
A tipple a day keeps the pain away Having between three and seven standard drinks a week seems to be the optimum amount for fending off a chronic pain condition that’s thought to affect one in 20 people worldwide. In a study in the journal Arthritis Research & Therapy, researchers found that moderate drinkers reported a lower severity of fibromyalgia symptoms than teetotallers or heavy drinkers. Too much alcohol reversed the effect. Similar results were seen for the quality of life scale including social functioning, vitality and general health. A standard drink in the US is equivalent to 355 millilitres of beer, 148ml of wine, or 44ml of distilled spirits.
Don’t stress, get over it Dwelling on stressful events can increase inflammation, say Ohio University researchers. It causes increased levels of C-reactive protein, which is mainly produced by the liver as part of the immune system’s initial inflammatory response to trauma, injury or infection. The protein is widely used as a clinical marker for one’s risk of disease later in life. In the study, 34 healthy young women were each asked to give a speech about their candidacy for a job to two interviewers in white lab coats, who listened with stonefaced expressions. Half the women were asked to contemplate their speech, while half were asked to think about neutral images and activities. The levels of C-reactive protein in drawn blood were significantly higher in those asked to dwell on the speech.
creates structural seams between the layers, which could burst when fluid is pumped through them at high pressure – as in the body’s blood vessels. The researchers designed 3-D filament networks in the shape of a vascular system that sat inside a mould. The mould and the vascular template were removed once cells were added to form a solid gel tissue around the filaments. To find the optimal material, the team tested different formulations using a simple material: sugar. Sugars are mechanically strong, so the printed 3-D network could be sufficiently rigid to support its own weight. In addition, the template could be easily dissolved and flow out of the gel construct, leaving a vascular architecture spread throughout the bioengineered tissue. “The perfect cylinders we are moulding into engineered tissues are similar to those that make up human blood vasculature,” says Dr Jordan Miller, the study’s lead author. To print the sugar network, the scientists modified a commercially available 3-D printer called RepRap to extrude molten sugar with high precision. Once the template was made, gels containing human cells were set around the sugar network to create tissue. The sugar was then dissolved, leaving a channel through which nutrient-rich media could be pumped to feed the cells inside. The team created a piece of liver tissue using human liver cells. “Our 3-D culture technique is able to create tissues in physiologically relevant architectures and at normal cell densities – tens to hundreds of millions of cells per millilitre – which allows us to explore cellular behaviour in a way that more closely mimics how cells grow in the body,” says Miller. Armed with this new technology, Miller and his colleagues are studying future possibilities. “We are investigating using this technique for making large-scale engineered tissues containing tens of millions of cells,” he says. “Liver tissue, heart tissue, and pancreatic tissue will continue to be areas for us to explore.” life@scmp.com
The availability of cheap antibiotics has saved many lives, but it has also created a severe public health problem. Patients and physicians may benefit in the short run by liberally prescribing and consuming antibiotics, but we would be better off if antibiotics were reserved for relatively serious infections. The diffusion of antibiotic-resistant bacteria into our environment is a predictable side effect of the widespread use of antibiotics – which some have described as a collective action problem. In contrast, using narcotics does not create a collective action problem since the costs and benefits are borne by the users themselves. Although many argue that recreational drug use harms non-users, most of the harm associated with these drugs – such as theft and murder – is caused not by drug use, but rather by the enforcement of drug laws. These laws create the conditions for black markets to flourish, for violence to be used and police corruption to thrive. The evidence from the only country to decriminalise personal possession of all recreational drugs, Portugal, suggests that consumption has not significantly increased for most drugs, and has declined for some. We should call off the war on drugs and consider more humane and less intrusive alternatives for helping drug addicts. There is a stronger justification to regulate the use of antimicrobial drugs instead. Yet in many countries antibiotics are sold over-thecounter and dispensed without thought for the consequences. We should think hard about how to regulate them in a way that balances individual liberty and public health. One person using an appropriate course of antibiotics may recover from an infection and prevent himself from becoming a vector. But he also increases the risk of harm to himself and others by increasing the prevalence of antibioticresistant bacteria in his own body and the environment. Thus, Margaret Battin at the University of Utah and her colleagues conclude that the choice to consume antibiotics “is partly a problem of prudence, of considering apparent short-term benefits against unknown but serious risks for oneself now and oneself in the future; and it is also a collective action problem, because the resistance one engenders in one’s own body may also affect others”. In economic terms, the collective action problem stems from the fact that the price of antibiotics fails to include the social cost of resistance. This distortion is exacerbated by health care systems in which
We should call off the war on drugs. There is a stronger justification to regulate the use of antimicrobial drugs instead third-party payers – including governments and health insurance companies – blind physicians and patients to the full cost of treatment. What, then, should be done to minimise the collective harm associated with antibiotic use? Educating patients and doctors about the nature and risks of antibiotics can go some way to reducing careless consumption. We should also phase out the use of antibiotics in farm animals, and forbid factory farming more generally. This would help preserve the efficacy of existing antibiotics for human use and reduce the threat of zoonotic viral infections such as avian flu and swine flu. For antibiotics to remain effective, we may also need to incentivise pharmaceutical firms to conserve existing drugs and encourage developing nations to ban over-the-counter sales of antibiotics. Wealthier nations should share information and surveillance technology with developing nations to monitor outbreaks of resistant pathogens. Battin et al suggest that we should simply “add a fixed amount, say a US$1 surcharge to every course of a first generation antimicrobial, and a slightly larger surcharge – say, US$2 – to each second generation antimicrobial course. Funds generated could be used to support antimicrobial research by the government directly or through grants and contracts”. Dr Jonny Anomaly is an ethicist from Duke University. This column is an abridged version of a recent article from the Journal of Medical Ethics.