Drug-eluting in vivo probe to monitor age-related lower bowel dysfunction

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Increasing age is frequently associated with a build-up of faeces in the large bowel due to difficult, infrequent and incomplete emptying of the bowel (chronic constipation) as well as leaking of bowel contents (feacal incontinence). These are known as age-related bowel disorders. Over one third of the over 65-year olds in the community and more than half of those in care homes will suffer these age-related bowel disorders. To the sufferer the symptoms can cause significant embarrassment, loss of dignity and quality of life. To the health service the cost of treating such conditions reached £1 billion in 2010. This age group is predicted to increase, where the number of people aged 65 and over will increase by more than 40 % within 20 years, making this a major social and economic problem. Therefore, there needs to be an approach that allows for the early detection of predictive markers of age-related bowel disorders so that effective treatment can commence at an early stage, delaying/preventing the onset of the disorder and extending healthspan.The movement of faeces through the large bowel requires the coordinated activity of the nerves and muscles that control this region. The outer most layer of the bowel known as the mucosa, has cells that can detect the contents present within our bowels and they release chemicals to communicate to the nerves to coordinate muscle contractions. We have shown that this communication process is altered with age as there are changes in the release of these chemicals. This in turn impairs the function of the muscles and results in a loss in the movement of faecal matter. Therefore, if we can measure the chemicals and the function of the muscle over time, we will be able to detect these changes very early before the patient gets symptoms and start treatments to delay/prevent the onset of these disorders.To meet these challenges, the first step will make an electrochemical probe that can be inserted into the lower bowel to track the changes in the chemicals released from the mucosa and the muscle activity. This will require optimising the design and the electronics to allow us to conduct the required measurements, Additionally, we would like our probe to be able to release drugs locally into the bowel so the device will be constructed with a tube within the probe to allow for this. To make these probes we will utilise 3D printing, which provides a platform for the efficient manufacturing of the parts of the probe. Additionally, this approach will allow us to scale this device, from the small probe developed as part of this study in rodents to a larger probe for use in future human studies. Once these probes have been made, we will explore how modifications to the materials used to construct the probe and the shape of the probe affect its performance. The best prototype will be used for investigations in animal models.Initially our probe will be inserted into the lower bowel of an anaesthetised mouse. These studies will allow us to map how chemicals are released in the lower bowel and how muscle activity varies in the regions measured. Additionally, we can explore the effects of different drugs in the lower bowel. These important studies will allow us to establish key protocols for our ageing studies. Using a mouse model which has similar age-related bowel dysfunction to that experienced in humans and where the bowel is regulated by many of the same chemicals used by humans provides us with an ideal model to carry out a longitudinal exploration of how mucosal chemicals and muscle activity change during the lifespan of an individual animal whilst simultaneously monitoring its faecal output as a marker of dysfunction. This will allow us to showcase how our probe can be an attractive tool for tracking and predicting the likelihood of age-related bowel disorders. Such findings will allow us to rapidly conduct clinical trials of our device in humans.