There is currently a timely opportunity to create dramatically improved green (renewable) and environmentally-friendly biodegradable materials for high volume, low load, and low cost. By manufacturing new bacterial cellulose reinforced bio-derived polymer nanocomposites, a new class of hierarchical composites with both much improved mechanical and environmental performance, as well as reduced through-life costs will be possible. The resulting product will be made completely from renewable resources, and will be totally biodegradable. We are expecting greatly improved materials for which three major applications are envisioned: fibre reinforced green nanocomposites for the automotive and construction industry and foamed nanocomposites as novel insulating materials for the packaging and construction industries.

One hundred and fifty ago, life expectancy in the UK was about 43 years. Improvements in nutrition, medicine and public health have dramatically increased this such that those born today can expect to live for over 80 years. This 150 year period is but the blink of an eye in evolution terms, and the evolution of our musculoskeletal system has not caught up with the increased life expectancy. It is therefore no surprise that musculoskeletal disorders are one of the biggest expenditures in the annual NHS budget (about £5.4bn). Our vision is for lifelong musculoskeletal health. We consider the only way to achieve this is to identify musculoskeletal problems early in life, then make small interventions to correct them before they become chronic. This preventative approach needs new technology which we will create using the equipment in the Medical Device Prototype & Manufacture Unit. We seek to manufacture early intervention implants using material that is tailored to make the surrounding bone stronger by controlling the bone strain experienced. We want to make smart instruments and implants that can measure biomarkers in synovial fluid to provide objective measures of joint health. We want to deploy new biomaterials like nanoneedles that can bypass the membrane of bacteria cells and provide anti-infection coatings on our implantable devices. We will manufacture ligament, tendon and capsule repair patches using a soft tissue 'velcro' fixation combined with functionalised surfaces that adhere to soft tissues on one side, yet provide a low friction sliding surface on the other side. We also want to better understand the ageing process of osteoporosis and the effects of bisphosphonate theory. Finally we want to perform higher fidelity laboratory testing of musculoskeletal tissues, both to understand better the pathology, but also the response of tissue to our proposed treatments. The proposed Medical Device Prototype & Manufacture Unit would enable breakthroughs in all these interrelated research themes. The powder bed fusion additive manufacture (AM) machine and 2-photon lithography AM machine allow manufacturing of porous lattice materials at the range of scales we need to create stiffness matched implants with 150 micron features down to microfluidic channels for our sensing technology and nanoneedles with sub-micron features. The nano CT scanner has a higher resolution (sub-micron) than currently available and the 3D microscope is equipped with confocal profiler with 100 nanometre resolution - these imaging instruments will allow unprecedented surface and internal imaging of pathological tissues and the response of tissues to our interventions. Our research will be conducted in an environment that will strongly encourage translation. The Prototype & Manufacture Unit will be set up with all the regulatory approval and quality control to enable us to manufacture devices from first off prototypes through to small batch production parts for early clinical safety studies. This combination of cutting edge AM and imaging equipment in an environment with strong emphasis on translation would enable us to break new ground in all our research themes and also bridge the gap between exciting laboratory testing and clinical practice.

Birefringence is a difference in refractive index that occurs along different axes in a material. In some materials this effect is intrinsic due to the atomic structure. In other materials, artificial birefringence can be induced by a mechanical stress that produces anisotropies in the material. Polarized waves travel at different velocities through the stressed regions depending on their polarization direction. This phenomenon is exploited in the well-established technique of photoelasticity, in which a model of the component of interest is made in an optically transparent plastic material and placed between polarizing optics. The induced birefringence is directly proportional to the stress experienced at a given point: contours of constant difference in the principal stresses and contours of the principal stress direction appear as fringe patterns. The technique has played a fundamental role in experimental mechanics, design and manufacturing. This project is concerned with measuring the stress-induced birefringence in materials that are opaque at visible wavelengths. We will use THz illumination between 0.3 and 1.5 THz where some fraction is transmitted through a range of non-polar materials including ceramics, plastics and composites. Measuring the stress-induced birefringence will provide information on the internal stress distribution in real components that are opaque at visible wavelengths, removing the need to model it in transparent plastic. This new unique stress visualisation technique might be considered as 'photoelesticity for opaque objects', although more accurate techniques will be used to measure the phase difference that arises between the polarized components of the illumination. Measurement from the real components also enables direct validation of numerical models. These new techniques will enable in-process control during manufacturing applications and in-service quality assurance, for a range of materials where this is not currently available, enabling step changes in the manufacturing processes used and the components that can be produced. This project will provide the underpinning research to determine if measuring stress-induced birefringence at THz frequencies is feasible. The phenomenon has not been reported in the literature. Based on the fundamental measurements of the stress-optic coefficients, THz systems will be built to measure residual stress distributions and stresses produced by direct loading in ceramic and polymer materials. Non-spectroscopic imaging at THz frequencies is not well developed, enabling novel phase measurement techniques to be implemented with single point detectors and start-of-the-art line detectors. The project brings together research expertise in optical instrumentation for industrially relevant metrology and industrial collaborators with strong track records in innovation for high value manufacturing applications.

Glioblastoma multiforme (GBM) is the commonest primary malignant brain tumour. Despite advances in chemotherapy, radiotherapy and surgical technology, the prognosis remains poor. Only a minority of patients are suitable for maximal treatment comprising surgical excision, radiotherapy and chemotherapy, and even following maximal treatment, average survival remains at approximately 14 months from diagnosis. There is no cure for GBM and patients inevitably suffer from recurrence and progression of the disease. The majority of tumour recurrences occur within 2cm of the site of the original tumour due to microscopic invasion of tumour cells into surrounding brain tissue which escape surgical excision and radiotherapy. One of the major obstacles to the effective treatment of brain tumours is the existence of the blood-brain barrier (BBB), which prevents the free passage of drugs from the bloodstream into the brain. It is sometimes possible to increase the amount of drug which enters the brain by using high drug doses, but this often results in severe side-effects which are unacceptable to patients. Our solution is to bypass the BBB by delivering chemotherapy directly to brain tissue surrounding the tumour following excision, using a neurosurgical technique called convection-enhanced delivery (CED). CED describes a method of direct drug delivery to the brain through ultrafine microcatheters. This technique allows us to target the chemotherapy to recurrent brain tumours with very high safety and accuracy, and to distribute effective drug concentrations throughout relevant areas of the brain. This approach also reduces the risk of side-effects by specifically targetting drugs to the brain. We have previously used this technique to deliver drugs to patients with Parkinson's Disease, and over the last 5 years we have been working with industrial collaborators to develop a CED catheter system which allows us to deliver repeated drug doses to the brain. In this project we propose to combine CED with recent advances in the field of nanotechnology. By encapsulating chemotherapies in biodegradable nanospheres our aim is to achieve controlled drug release within the brain, to reduce the drug doses required to achieve tumour regression, and to limit the risk of side-effects. We have chosen a nanosphere formulation which is widely used in the medical industry and is proven to be safe and non-toxic. We have approval for a clinical trial of CED of unencapsulated chemotherapy, and this study represents a logical progression. By using CED to deliver chemotherapy nanoparticles to the brain we hope to reduce tumour recurrence and progression and to improve the quality of life of patients with this devastating disease. Our research team comprises a unique collaboration between neurosurgeons, neuroscientists, chemists and chemical engineers with the knowledge and experience to develop this novel technology for patient benefit.

There is a growing need for clinicians to be able to diagnose and prescribe therapy according to an individual's healthcare needs and potential responses. To allow this personalised medicine approach to be fulfilled, new technologies allowing rapid and accurate detection of biomarkers indicative of specific diseases are needed and to be available to clinicians to aid in their management of disease. This proposal aims to bring together physical scientists working on nanoparticles capable of detecting biomarkers at ultralow concentrations with information technologists capable of interpreting and presenting data from these complex assays to the clinical partners who are interested in how best to utilise this new information in improved healthcare practice. The basis of the proposal is to create an in vitro diagnostic assay at first which is capable of detecting multiple biomarkers in a patient's sample which allows the clinician to produce a risk profile of the patient. A second aspect of the research is to investigate in vivo imaging by SERS for specific biomarkers and in a multiplexed manner. The disease we are targeting is cardiovascular disease which covers atherosclerotic plaques. Risk of atherosclerosis is identified by increased levels of specific biomarkers, however, atherosclerosis is characterised by a localised rather than a systemic immune response. Therefore the measurement of biomarkers for in vitro prediction will be investigated in parallel to quantification of vascular inflammation and the development of a therapeutic approach to convey treatments directly to the affected vessel. The assays will be based on surface enhanced Raman scattering (SERS) and use metallic nanoparticles. The output will be in the form of a vibrational spectrum which will contain a high degree of information relating to the relative quantitation of each of the specific biomarkers being investigated. Two types of in vitro assay will be investigated with one of them carrying forward for in vivo imaging. The in vivo assay will recognise the target and through interpretation of the signal allow a decision to be made whether to induce a therapeutic action. The action we are proposing is a photothermal response from an assembly of the nanoparticles triggered by the specific biomarker being interrogated. This makes the response highly specific to that biomarker and will offer a new way to manage atherosclerosis.