Definition: A rapidly developing area at the interfaces of engineering/physical sciences, life sciences and medicine. Includes:- cell therapies (including stem cells), three dimensional cell/ matrix constructs, bioactive scaffolds, regenerative devices, in vitro tissue models for drug discovery and pre-clinical research.Social and economic needs include:Increased longevity of the ageing population with expectations of an active lifestyle and government requirements for a longer working life.Need to reduce healthcare costs, shorten hospital stays and achieve more rapid rehabilitationAn emergent disruptive industrial sector at the interface between pharmaceutical and medical devicesRequirement for relevant laboratory biological systems for screening and selection of drugs at theearly development stage, coupled with Reduction, Refinement, Replacement of in vivo testing. Translational barriers and industry needs: The tissue engineering/ regenerative medicine industry needs an increase in the number of trained multidisciplinary personnel to translate basic research, deliver new product developments, enhance manufacturing and processing capacity, to develop preclinical test methodologies and to develop standards and work within a dynamic regulatory environment. Evidence from N8 industry workshop on regenerative medicine.Academic needs: A rapidly emerging internationally competitive interdisciplinary area requiring new blood ---------------------

The Cranfield IMRC vision is to grow the existing world class research activity through the development and interaction between:Manufacturing Technologies and Product/Service Systems that move UK manufacturing up the value chain to provide high added value manufacturing business opportunities.This research vision builds on the existing strengths and expertise at Cranfield and is complementary to the activities at other IMRCs. It represents a unique combination of manufacturing research skills and resource that will address key aspects of the UK's future manufacturing needs. The research is multi-disciplinary and cross-sectoral and is designed to promote knowledge transfer between sectors. To realise this vision the Cranfield IMRC has two interdependent strategic aims which will be pursued simultaneously:1.To produce world/beating process and product technologies in the areas of precision engineering and materials processing.2.To enable the creation and exploitation of these technologies within the context of service/based competitive strategies.

The aim of this Fellowship is to research and develop tissue-engineered chordae tendineae and leaflets for mitral valve reconstruction in the heart. Mitral valve stenosis and mitral valve regurgitation are the most significant and frequent causes of valve dysfunction in the mitral position in the heart. Regardless of the nature (acquired or congenital) and underlying cause of mitral valve dysfunction, a number of common changes occur in the valve components. These include deformation, tethering, tissue thickening and/or calcification, fusion, retraction, stretching, dilatation, or rupture. Conventional therapies for mitral valve dysfunction most frequently focus on the repair or replacement of the valve. Mitral valve repair is the gold standard for mitral valve dysfunction and usually employs synthetic biomaterials or chemically treated tissue, such as pericardium, taken from donors. Both approaches only deliver inert or biocompatible material solutions that cannot regenerate or grow with the patient, and may, subsequently calcify, become rigid and eventually degenerate. Ideally, surgeons would prefer tissue taken from the patient (autologous), since it will retain viability and regenerate. In most cases, however, autologous tissue is not available, and even if it is available, this is not an ideal solution. Functional tissue engineering (FTE) is an attractive alternative, which employs scaffolds repopulated with appropriate cells taken from the indented patient, and physically conditioned in the laboratory with a view to producing viable replacement tissues with appropriate functionality prior to implantation, which will have the potential to regenerate in the patient. The intention of this multidisciplinary project is to develop and evaluate FTE simulation systems that will deliver dynamic cell culture conditions to appropriate natural tissue matrices repopulated with cells, to investigate how the biomechanical and biochemical environment can direct the development of mitral tissue-equivalents in the laboratory. The approach of this Fellowship to tissue engineering of the mitral valve involves the use of tissue matrices of both human and porcine origin that have been treated to remove the immunogenic cells, reseeded with the patient's own cells and physically conditioned in the laboratory, in order to produce biological and biomechanical functionality of the graft prior to implantation. This will create an immediate regeneration potential in response to the cyclic loading in the body. The use of decellularised-only matrices in reconstructive surgery does offer an alternative approach and will be investigated. The proposed research postulates that simulation of the type of mechanical strain that mitral tissue encounters in the body will stimulate the cells to produce tissues with similar properties in the laboratory. In particular it is hypothesised that cyclic uniaxial tensile strain will produce mitral valve chordae-equivalent tissue while biaxial cyclic strain will generate mitral valve leaflet-equivalent tissue.