Of all places to have an injection, the eyeball is probably near the bottom of anybody’s list. Yet this is how macular degeneration – the leading cause of sight loss in the developed world – is commonly treated.
Individuals who have macular degeneration will have blurred or no vision in the center of their visual fields (as shown above).
In the UK, nearly 1.5m people are affected by macular disease, according to the Macular Society. In its commonest ‘wet’ form, macular degeneration is caused by the growth of rogue blood vessels at the back of the eye, due to over-production of a protein called vascular endothelial growth factor (VEGF).
The blood vessels leak, causing damage to the central part of the retina – the macula – and a loss of central vision. Regular injections of so-called anti-VEGF drugs help to alleviate the problem.
As well as being time-consuming, these injections can be stressful and upsetting for sufferers, many of whom are elderly. Because the condition is prevalent among older people, it is usually referred to as age-related macular degeneration, or AMD.
However, a number of emerging treatments – including eye drops, inserts and a modified ‘contact lens’ – could spell the end of regular injections, and treat the condition less invasively.
Anatomy of the eye. Video: Handwritten Tutorials
At the same time, emerging stem cell therapy, which has reversed sight loss for two patients with the ‘dry’ form of macular degeneration, could find wider use within a few years.
A shortage of donor organs for transplant surgery is fueling research to develop artificial livers and hearts, but how closely do they match up to the real thing?
Liver failure due to alcohol abuse, drug overdose and hepatitis is a growing problem. In 2016, 1220 Americans died waiting for a liver transplant, with the cost of treating cirrhosis – late stage liver scarring – is estimated at nearly $10bn/year.
‘In 2017, if you have liver failure, we don’t have a backup system,’ says Fontes. ‘But my group has a potential backup system. We are not ready for prime time yet, but we’ve some really good data.’
Liver failure can be hereditary or caused by excessive drinking. Image: Pixabay
Transplant surgeon Paulo Fontes at the University of Pittsburgh, US, regularly meets patients who ask what their options are aside from a liver transplant.
His group has attempted to build a new bioartificial liver, by seeding liver cells onto a liver scaffold. However, others working in this area have so far met with little success.
Now Fontes, working at the Starzl Transplantation Institute, has hit on a different strategy: to grow mini livers in living organisms. The work is in collaboration with Eric Lagasse, a stem cell biologist at the University of Pittsburgh, who showed lymph nodes are excellent ‘bioreactors’ for growing different types of cells, including liver cells.
The liver – made up of hepatocytes – has the capacity to regenerate after surgery. Image: Ed Uthman/Flickr
Lymph nodes filter damaged cells and foreign particles out of the body’s lymph system, which transports fluids around the body. When someone is ill, T cells from the immune system move to the lymph nodes to be cloned and released back to the bloodstream en masse to take on the microbe causing the illness.
For the past five years, Fontes and Legasse have been working with large animal models, infusing hepatocytes into the lymph nodes of pigs. ‘Within two months, it is amazing, but you have mini livers in the lymph nodes,’ he explains. ‘When you compare the mini liver with normal livers, they look very similar.’
Pigs are common animal models as they have similar organ systems to humans. Image: Pixabay
The mini livers weigh a few grams and would not offer a complete replacement for failed livers, but rather a supplement of liver tissue in patients with end stage liver disease who are too sick to undergo a transplant.
‘A lot of these patients have significant heart and lung problems, so would not sustain a full transplant,’ says Fontes. ‘The idea is to sustain their life by increasing their liver mass by creating new small ectopic livers within their lymph nodes.’
Compared with artificial livers, artificial heart technology is much further along the road to the clinic. To date, around 2000 artificial hearts have been implanted in patients, with demand driven similarly by an acute shortage of donors.
‘We wanted an artificial heart very similar to the natural human heart,’ explains Nicolas Cohrs at ETH Zurich in Switzerland. ‘Our hypothesis is that when you mimic the human heart in function and form you will have fewer side effects.’
Cohrs and his colleagues aim to print their artificial hearts so that they fit precisely into an individual patient. This is not yet close to clinic, but promises a tailored heart.
‘We take a CT scan of a patient, put it in a computer file and design an artificial heart around it, so it closely resembles the patient heart,’ says Cohrs. ‘We use these 3D printers and print a mould in ABS [acrylonitrile butadiene styrene], which is the plastic Lego is made of, fill it with silicone and then dissolve the mould with acetone to leave behind the silicone heart.’
Testing a soft artificial heart. Video: ETH Zurich
The plastic heart deflates and inflates with pressurised air. The first-generation device, made from silicone, has two chambers but survived for only 2000 beats. ‘This is only half an hour, so there is a lot of improvement needed,’ adds Cohrs.
A new prototype made from a more resistant [so far, undisclosed] polymer has managed more than a million beats, which is the equivalent of 10 days for a human heart. The goal is to develop a four-chamber heart that beats for 10 years, so a lot more work is still needed.
Around 10 million medical devices are implanted each year into patients, while one-third of patients suffer some complication as a result. Now, researchers in Switzerland have developed a way to protect implants by dressing them in a surgical membrane of cellulose hydrogel to make them more biocompatible with patients’ own tissues and body fluids.
‘It is more than 60 years since the first medical implant was implanted in humans and no matter how hard we have tried to imitate nature, the body recognises the implant as foreign and tends to initiate a foreign body reaction, which tries to isolate and kill the implant,’ says Simone Bottan at, who leads ETH Zurich spin-off company Hylomorph.
Hylomorph is a spin-off company of ETH Zurich, Switzerland. Image: ETH-Bibliothek@Wikimedia Commons
Up to one-fifth of all implanted patients require corrective intervention or implant replacement due toan immune response that wraps the implant in connective tissue (fibrosis), which is also linked with infections and can cause patients pain. Revision surgeries are costly and require lengthy recovery times.
The new membrane is made by growing bacteria in a bioreactor on micro-engineered silicone surfaces, pitted with a hexagonal arrangement of microwells. When imprinted onto the membrane, the microwells impede the formation of layers of fibroblasts and other cells involved in fibrosis.
25,000 people in the UK have a pacemaker fitted each year. Image: Science Photo Library
The researchers ‘tuned’ the bacteria, Acetobacter xylinum, to produce ca 800 micron-thick membranes of cellulose nanofibrils that surgeons can wrap snuggly around implants. The cellulose membranes led to an 80% reduction of fibrotic tissue thickness in a pig model after six weeks, according to a study currently in press. Results after three and 12 months should be released in January 2018.
It is hoped the technology will receive its first product market authorisation by 2020. First-in-man trials will focus on pacemakers and defibrillators and will be followed by breast reconstruction implants. The strategy will be to coat the implant with a soft cellulose hydrogel, consisting of 98% water and 2% cellulose fibres.
The membrane will improve the biocompatibility of implants. Video: Wyss Zurich
‘Fibrosis of implantables is a major medical problem,’ notes biomolecular engineer Joshua Doloff at Massachusetts Institute of Technology, adding that many coating technologies are under development.
‘[The claim] that no revision surgery due to fibrosis will be needed is quite a strong claim to make,’ says Doloff, who would also like to see data on the coating’s robustness and longevity.
The silicone topography is designed using standard microfabrication techniques used in the electronics industry, assisted by IBM Research Labs.