As part of the BBSRC's priority to enhance the Cell Supply Chain (Engineering and Biological Systems Committee) we wish to investigate methods of improving the interactions between biomaterials and mesenchymal stem cells. The use of mesenchymal stem cells in orthopaedic applications is established in the use of bone marrow aspirate and more recently in the use of isolated, purified and expanded homogenous cell populations. Within the body, the local niche within which mesenchymal stem cells reside is important in maintaining the cell phenotype. In response to injury the stem cell niche changes and the cells are stimulated to play a central role in bone repair. Future success of medical applications of mesenchymal stem cells will be dependent on the delivery of cells into the body in a manor that recreates a suitable niche to maintain cell viability and to boost regeneration. To underpin this work we wish to use BBSRC funding to explore how the surfaces of injectable cell delivery systems can be modified to stimulate appropriate cell adhesion and subsequent activities. Cell delivery systems are a new class of biomaterials that carry stem cells into the body and then create a 3D porous environment around the cell population. The biomaterial is normally highly porous and therefore presents a massive surface area to the cell population. The available surface can be engineered to present whole proteins and peptides that bind to specific integrin receptors. Other growth factor mediated effects on cells can also be stimlated with such a surface engineering approach. The student supervisor will be Professor Kevin Shakesheff, School of Pharmacy, The University of Nottingham. Under this project the student will collaborate with Ms Brigitte Scammell (Orthopaedic Surgeon and Academic) to isolated and characterise human mesenchymal stem cell populations. Following a careful literature review the student will surface engineer polymer surfaces with peptides that bind to the cells (this builds on work by Professor Shakesheff in collaboration with the University of Southampton, BONE 29 (6): 523-531 DEC 2001). The ability to augment osteoconductive behaviour (with additional ceramic components added to the biomaterial) will be used as in vitro quantification methodology. The student will work with Ms Scammell to develop animal models to quantify the effect of surface engineering on angiogenesis and bone repair.

Regenerative medicine (RM) is a convergence of conventional pharmaceutical sciences, medical devices and surgical intervention employing novel cell and biomaterial based therapies. RM products replace or regenerate damaged or defective tissues such as skin, bone, and even more complex organs, to restore or establish normal function. They can also be used to improve drug testing and disease modelling. RM is an emerging industry with a unique opportunity to contribute to the health and wealth of the UK. It is a high value science-based manufacturing industry whose products will reduce the economic and social impact of an aging population and increasing chronic disease.The clinical and product opportunities for RM have become clear and a broad portfolio of products have now entered the translational pipeline from the science bench to commercialisation and clinical application. The primary current focus for firms introducing these products is first in man studies; however, success at this stage is followed by a requirement for a rapid expansion of delivery capability - the 'one-to-many' translation process. This demands increasing attention to regulatory pathways, product reimbursement and refinement of the business model, a point emphasised by recent regulatory decisions demanding more clarity in the criteria that define product performance, and regulator initiatives to improve control of manufacturing quality. The IMRC will reduce the attrition of businesses at this critical point in product development through an industry facing portfolio of business driven research activities focussed on these translational challenges. The IMRC will consist of a platform activity and two related research themes. The platform activity will incorporate studies designed to influence public policy, regulation and the value system; to explore highly speculative and high value ideas (particularly clinically driven studies); and manufacturing-led feasibility and pilot studies using state of the art production platforms and control. The research themes will focus on areas identified as particular bottlenecks in RM product translation. The first theme will explore the delivery, manufacturing and supply processes i.e. the end to end production of an RM product. Specifically this theme will explore using novel pharmaceutical technology to control the packaged environment of a living RM product during shipping, and the design of a modular solution for manufacturing different cell based therapies to the required quality in a clinical setting. The second research theme will apply quality by design methods to characterise the quality of highly complex RM products incorporating cells and carrier materials. In particular it will consider optical methods for non-invasive process and product quality control and physicochemical methods for process monitoring.The IMRC will be proactively managed under the direction of a Board and Liaison Group consisting of leading industrialists to ensure that the Centre delivers maximum value to the requirements of the business model and assisting the growth of this emerging industry.

The Innovative Manufacturing and Construction Research Centre (IMCRC) will undertake a wide variety of work in the Manufacturing, Construction and product design areas. The work will be contained within 5 programmes:1. Transforming Organisations / Providing individuals, organisations, sectors and regions with the dynamic and innovative capability to thrive in a complex and uncertain future2. High Value Assets / Delivering tools, techniques and designs to maximise the through-life value of high capital cost, long life physical assets3. Healthy & Secure Future / Meeting the growing need for products & environments that promote health, safety and security4. Next Generation Technologies / The future materials, processes, production and information systems to deliver products to the customer5. Customised Products / The design and optimisation techniques to deliver customer specific products.Academics within the Loughborough IMCRC have an internationally leading track record in these areas and a history of strong collaborations to gear IMCRC capabilities with the complementary strengths of external groups.Innovative activities are increasingly distributed across the value chain. The impressive scope of the IMCRC helps us mirror this industrial reality, and enhances knowledge transfer. This advantage of the size and diversity of activities within the IMCRC compared with other smaller UK centres gives the Loughborough IMCRC a leading role in this technology and value chain integration area. Loughborough IMCRC as by far the biggest IMRC (in terms of number of academics, researchers and in funding) can take a more holistic approach and has the skills to generate, identify and integrate expertise from elsewhere as required. Therefore, a large proportion of the Centre funding (approximately 50%) will be allocated to Integration projects or Grand Challenges that cover a spectrum of expertise.The Centre covers a wide range of activities from Concept to Creation.The activities of the Centre will take place in collaboration with the world's best researchers in the UK and abroad. The academics within the Centre will be organised into 3 Research Units so that they can be co-ordinated effectively and can cooperate on Programmes.