Stem Cell Expansion in a Fluidised Bed Bioreactor for Accelerated Osseointegration of Bone Substitute Material

Maintenance of an active lifestyle has many health benefits for society, but one drawback is an increase in the number of joint replacements and subsequent revisions of these, plus other orthopaedic interventions, such as bone grafts in complicated fractures or dental procedures, that become necessary with increasing longevity. There are over 70,000 total hip replacements and 73,000 total knee replacements carried out in the UK each year. The current demographics indicate an increasing aging population. In addition to this, joint replacements are being carried out on younger patients the number of replacements and therefore revisions will continue to rise.The gold standard material used in revision of joint replacements is allograft (bone from other hip replacements), but there are growing concerns with its use, such as disease transmission. The gold standard for bone grafts is autograft (bone from the patient), but harvesting it is not without risks and can result in pain at the donor site some years post-operatively. In all cases a limitation is the availability of grafting material. Synthetic ceramic materials are commercially available. Development of a graft material which is a combination of a synthetic ceramic material with a cell population to accelerate the healing process has great potential, with application in all areas where bone substitute is needed for repair and replacement, and if reached will result in improved post-operative quality of life, health and wellbeing. This proposal will develop technology to provide a synthetic bone graft material containing a population of bone-forming cells (stem cells from bone) to improve the osseointegration (the process of bone cells populating the bone graft and integrating it with the patient's own bone). The technology is a fluidised bed bioreactor to culture the stem cells on highly porous ceramic particles. The fluidised bed bioreactor will be designed to provide the ideal environment to obtain particles containing a maximum population of stem cells. Experimental and computational research will be carried out to provide the operating information for the bioreactor to ensure the quality of the stem cell population in the packing material.

The primary beneficiaries of this research fall into three broad groups - the patients; the surgeons; the NHS & the UK economy. Any patient in need of orthopaedic or dental surgery to replace or repair bone damaged as a result of trauma or disease will directly benefit from this research. Development of the technology to provide a reliable, reproducible, synthetic material which has enhanced bone healing properties, has obvious advantages over the current alternatives where there are real issues in relation to the harvesting of autograft and potential disease transmission from allograft. The new technology will improve the quality of life and health of the patient by enhancing the bone response and allowing faster recovery times. The need for a donor site for the removal of allograft bone will also be reduced. This is of significant benefit to the patient as it has been reported that the donor site in one third of patients is still painful three years postoperatively. The surgeons will also be primary beneficiaries as the need for a reliable alternative to human bone graft is widely recognized. Harvesting of allograft is time consuming and results in a limited amount of bone graft from a site which has long term pain relates issues as described above. The technology will improve the effectiveness of the orthopaedic and dental procedures resulting in substantial savings for the NHS if the healing process is improved, is more rapid and ultimately fewer revision procedures will be required. Direct benefits to the NHS would be improved surgical outcomes which would enhance the postoperative recovery of patients. This would also impact all levels of staff from surgeons through to nurses and other support staff such as physiotherapists and occupational therapists who would benefit from healthier and happier patients. The introduction of the technology could therefore have a significant economic impact on NHS budgets when all aspects of patient care are considered. The successful development of the technology will keep the UK at the cutting edge of developments in the field of bone substitute materials. It is anticipated that private sector companies will be interested in commercialization of the technology. The benefits will begin within the three years of the project and are predicted to be fully realised within 7-10 years. Communication and engagement with the academic and clinical community will be made through the applicants' involvement in the University of Bath's Centre for Regenerative Medicine, the Centre for Orthopaedic Biomechanics and the SetSquared Initiative, which brings together researchers, clinicians and industrialists on a quarterly basis, but also provides a network of contacts. Dr Irene Turner has established industrial links and these could provide opportunity for commercialisation of the technology. In the case that there are patent opportunities as a result of the work, the applicants will seek the support of Bath Ventures who provide the assistance to obtain IP. The applicants are and will continue to be involved in outreach activities for the wider public. Dr Marianne Ellis and her group regularly engage in local science festivals and school engineering taster days, and with the support of the Corporate Communities Services she will take opportunities to give public lectures at the Bath Royal Literary and Scientific Institution, well attended by the age group this technology will most benefit, and the Bath Science Caf as well as podcasts, radio and TV interviews.