Hybrid approaches to tissue engineering

Our life expectancy is increasing and we are outliving our skeletal tissues. There is a need for orthopaedic surgery to move from replacement of tissues to regeneration. To do this medical devices are required that can stimulate the body's own healing mechanisms. Over the last 10-15 years, tissue engineering has promised that combining engineering principles with cells will lead to regeneration of tissues, however skin is the only tissue engineered product used clinically. The reasons skeletal tissue engineering has not been successful is that materials have not been developed that fulfill all the engineering design criteria for regenerative device (scaffold) and how materials interact with cells is not fully understood. A new hybrid approach is proposed where hybrid refers to an integrated interdisciplinary approach and the innovation in materials engineering that is needed. New materials must be developed that mimic the mechanical properties and structure of natural tissues. The aim is to build an interdisciplinary research team that can deliver high impact step changes in the way tissue engineering research is carried out to make skeletal tissue engineering a clinical reality. Team members will have expertise in materials chemistry and processing, multi-scale characterisation, materials modelling, cell biology, orthopaedic surgery and technology transfer. The adventurous programme will benefit the UK by improving the quality of life of patients, increasing the efficiency of orthopaedic surgery, reducing surgical costs and boosting the UK economy by ensuring patients recover and return to work more rapidly.The core platform technology will be novel nanostructured (hybrid) materials that can be designed to stimulate bone growth or cartilage regeneration before they are remodelled in the body and replaced by natural healthy tissue. To make these complex materials a clinical reality they must be understood from the atomic through the nano to the macro level and optimised with respect to cellular response. Computer models and improved characterisation methods are needed. Bone scaffolds must stimulate stem cells to produce bone and new ways of growing cells in devices may be necessary in order for blood vessels to grow throughout bone scaffolds and for cartilage regeneration to become a reality. If new devices are to reach the clinic, technology transfer must be considered. My vision is to build and lead a world renowned research group successful in musculoskeletal tissue engineering with a new field of inorganic/ organic hybrid materials engineering at its core. The research group will attract best, internationally leading researchers to the UK (or to stay in the UK). It will involve international and UK collaborators, with the UK at the focus, placing it at the forefront of biomaterials and tissue engineering. There will be focus on developing a dynamic and supportive research environment and on developing the career of group members so they will become the next leaders of the new fields that will evolve from the group's work.

There are several target groups that will benefit directly from this research. Orthopaedic, neurological and plastic surgeons, patients and health services (e.g. the NHS) will benefit as end users. Patients and UK economy will benefit as patients recover more rapidly and to a fuller extend, allowing them to return to work more rapidly. Medical device companies will benefit from potentially market leading products and new tools for their quality assurance. Currently, the NHS performs 60 000 hip (600 000 worldwide) and 70 000 knee replacements (>1M wordwide) annually due to degenerating cartilage. Unfortunately the implants eventually fail (usually after 15-25 years) and revision operations are common, causing patients intense pain and lack of mobility. Revision operations cost the NHS 2-3 times that of the initial operation. This research programme has the potential to create devices that can regenerate diseased cartilage so that the number of joint replacements and therefore revision operations are drastically reduced. 25 000 bone graft operations are carried out in the UK annually (>1M worldwide). Current best practice for surgeons is to take bone from the pelvis and move it to the defect (autograft). Problems are that the supply of bone is limited and there is donor site morbidity. After the operation, the pelvis is extremely painful, recovery time is long (4 weeks to 6 months) and 46% of people have complications that require further treatment, many needing revision operations. Autograft procedures also require two clinicians in theatre. There is therefore a clinical need for synthetic grafts that regenerate bone defects to healthy natural bone. Orthopaedic surgeons require a new device that is a porous construct that stimulates bone growth but is tough and has some flexibility. Surgeons also want to be able to cut the device to shape during the operation and be press-fit into bone defects.These devices will reduce recovery time by stimulating the regenerative process, thereby improving healing rate and removing the need to harvest the bone before implantation, reducing operation time, which will save the NHS 100M per year alone. A reduction in associated secondary disease treatment is particularly pertinent in the context of the UK's aging population, who will benefit from improved the quality of life, reducing the burden on a heavily overloaded social care system. The devices for bone regeneration have the potential to fill 10-15% of the $500M global market. If successful cartilage regeneration to be achieved, the market would be significantly higher. Companies must invest in the materials and take them through regulatory approval. The intellectual property generated will be filed by Imperial Innovations and licensed by the collaborating companies, e.g. RepRegen Ltd., (London), contributing to the growth of the UK's strategically important biosciences industry. They will also form partnerships with larger medical device companies (e.g. NovaBone and Stryker), increasing the adoption rate of the new materials. To ensure that the materials are designed to meet the end user's needs, I have collaborations with leading surgeons within the Imperial College Medical School with whom I meet regularly to discuss their needs and latest results. Progress will be communicated to other surgeons via presentation sessions and through high impact publications. Progress will be communicated to the general public by building on my current media contacts, having recently given interviews to BBC Radio and the Daily Mail. The Victoria and Albert Museum will benefit as they have included a scaffold in their new permanent exhibition of ceramics. Outreach activities, in conjunction with Lord Robert Winston's Outreach Laboratory, will encourage more high quality students to join the fields of materials science and engineering and tissue engineering and aim to increase the number of female scientists.