Novel bioengineering for auto-integration of advanced cell delivery substrates

According to the World Health Organisation age-related macular degeneration (AMD) is the third most prevalent cause of blindness worldwide, and the leading cause of blindness in industrialised countries. There are two types, the neovascular - which contributes to 10% of cases - and atrophic - which contributes to 90% of cases. In AMD, a section of the retina called the Bruch's membrane thickens with age and can interfere with the waste/nutrient exchange between the retinal pigment epithelial (RPE) cells - the layer upon which photoreceptor cells attach and survive - and the choroid - the intricate network of vessels responsible for blood supply. This interference can cause the retinal pigment epithelial cells to die, which in turn can lead to photoreceptor cell death, eventually causing irreversible central vision loss. The sufferer loses their independence as this prevents them from carrying out everyday tasks such as reading and driving. The main risk factor for AMD is age and it, predominantly, affects people over the age of 50. It has already been reported by clinicians that cases of AMD have doubled between the years of 2000-2010, and with the population living longer the prevalence of this disease is anticipated to rise to more than double by the year 2030. Considering there is no current treatment for atrophic AMD and with its prevalence on the rise, this important issue needs to be addressed now.

A number of studies report the use of substrates to deliver healthy RPE cells under the photoreceptor cells before they begin to die. They discuss placing the substrate on top of the diseased Bruch's membrane to deliver a monolayer of RPE cells. I believe that simply placing a novel substrate on top of the diseased membrane could exacerbate the issue. The problem in AMD is the thickened Bruch's membrane, so adding a further layer could further increase the nutrient/waste exchange path leading to damage to the transplanted cells. I hypothesise that a cell transplant substrate can be designed that will unblock the diseased Bruch's membrane while providing support for the healthy RPE monolayer thus leading to improved nutrient/waste exchange between the photoreceptors and the choroidal blood vessels.

This project will develop a novel bioengineered persistent substrate with a bioactive layer that will deliver active molecules at a controlled rate. It will deliver the required monolayer of RPE cells in order to ensure photoreceptor cell survival while simultaneously removing and replacing the diseased native Bruch's membrane. These prerequisites address the necessity of having a permanent membrane upon which the retinal pigment epithelial cells can attach and survive, the removal of the diseased tissue, and the integration of the permanent substrate to replace the diseased Bruch's membrane in order to ensure that the optimal exchange pathway thickness is maintained.

I believe this novel approach will contribute to improving quality of life by reducing the number of people who lose their independence and require assistance/intervention due to AMD. The project aligns to the key Life Sciences Industrial Strategy challenge of developing advanced therapeutics under the theme of healthy ageing in the Health Advanced Research Programme and contributes to the EPSRC Healthy Nation delivery plan ambitions.

This research will help people who develop AMD to maintain their independence and improve their quality of life. It will in turn contribute to the healthcare system by delivering a one-time treatment for people with AMD. The NHS is already under an immense amount of pressure pertaining to the on-going healthcare of the ageing population. This one-time treatment will give back the independence and freedom to these patients, and ease some of the pressure on the NHS by reducing the assistance and treatment required by those that suffer from AMD.

It will contribute to the UK's commercial sector by creating industrial collaborations and new jobs with expertise in medical devices. It will contribute to the economic growth of the UK, as this project will develop state of the art expertise and innovation based in the UK with a vision of exporting the product globally. This project requires many different experts to work together, therefore allowing the forging of multidisciplinary collaborations in order to develop the medical device. The translational nature of the project dictates that it will require the contribution of the commercial sector and hence will train people within the area of medical device development outside the academic profession. This project may also contribute to the development of a new spin-out company thereby commercialising novel scientific knowledge with application to other sectors in the medical field.