Smart materials for targeted stem cell fate and function in skeletal repair

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Bone disease and injury are burgeoning in our ageing populations, leading to a high economic and social cost. Treatments for bone injury are often ineffective or inappropriate. Autograft may be limited in supply and causing morbidity at the donor site, whereas allogeneic material may be poorly osteoinductive or of unreliable efficacy and in some cases may act as an agent for the transmission of life-threatening infectious disease. To address these challenges, we propose to develop a new tissue replacement that augments bone formation through temporal and targeted delivery of chemical cues for bone induction.

To achieve this we will build on an existing collaboration between the universities of Edinburgh and Southampton focused on developing a new generation of biomaterials for bone regeneration. We will first engineer polymer nanoparticles which can carry a range of chemical cues (growth factors, small molecules, nucleic acids) and which degrade at controlled, predetermined rates. We will test this by examining release of fluorophores and by measuring uptake of released dyes by cells in in vitro assays. Next, we will use couple chemistries to tether such nanoparticles to the backbone of a variety of hard and soft tissue scaffolds. In this way, the scaffolds will provide an environment for cell in growth and will provide a reservoir of heterogeneous factors that are released at the appropriate times for the appropriate cell populations. Finally we will test the efficacy of such scaffolds in ex vivo models, such as the chorioallantoic membrane of the chick egg, and in in vivo small animal defect models. We take full advantage of the high-resolution CT imaging facilites available at Southampton to track drug delivery and tissue healing.

Our approach will provide a new technology for controlling - temporally and spatially - the delivery of factors from hard and soft tissue scaffolds. This will enable the controlled redevelopment of tissues following injury.

Our research project aims to bring together a multidisciplinary team to develop a new technology for improving tissue regeneration, and will have a number of academic, industrial, societal, economic and awareness impacts.

UK PLC: UK Healthcare must reap the dividend of the current 'revolution' in regenerative medicine/science. This research programme will deliver new leading-edge multi and cross-disciplinary research in exciting and highly translatable areas of biology and chemistry.

Training: A central part of our agenda is to break down traditional 'barriers' between physical and biomedical sciences. The PDRA's will benefit immensely from the interdisciplinary, translational thrust of the programme and the cross-fertilisation. They will gain a wide variety of both "hard and soft" skills that will be readily applied in a variety of employment sectors.

Business and Industry: The applicants have major interactions with industry, and have direct personal experience of spin-off/spin-out companies. As the programme progresses new commercial opportunities will undoubtedly arise - prospects in the global healthcare arena will be significant and we will look to translate our unique scaffold approaches through to the clinic in regenerative projects, programmes as appropriate including the UK Regenerative Medicine and Medical Technologies Innovation and Knowledge Centre programmes.

General: Our multidisciplinary programme will provide many opportunities for involvement in public engagement and dissemination. Research fellows will participate at the International Science Festivals and become involved in a variety of out-reach activities such as the locally run 'Researchers-in-Residence Programme' which places PDRA's in local secondary schools allowing the public to benefit, as well as engaging the next generation of scientists. We will also engage with the Cell Therapy Catapult as appropriate especially from a stem cell clinical translation perspective in the end phase of our programme again as appropriate (preclinical and early clinical development).