Title: Development of Prototype Device for Minimally Invasive Delivery of Osteospheres for Treatment of Osteoporosis (MIDOs)
Funder: Department of Health and Social Care

Abstract: To take this technology forward for clinical evaluation and commercialisation activities, the following development plans need to be implemented: 1) Confirm efficacy of scale-up manufacturing and conduct technical feasibility studies for alternate applications; 2) Experimental Modelling validation of technology and application with carrier media in situ; 3) Development of a prototype minimally invasive delivery device; 4) Health Economic evaluation of technology proposed; 5) all the above will be supported by a clinical Patient Public Involvement (PPI) study including patients, carers and health care professionals evaluating use of the technology and potential population numbers at risk of fracture from osteoporosis. Scale-up efficacy would be achieved by preparing and manufacturing a minimum of 1kg of bulk and 1kg of porous microspheres and evaluating the time, amount and cost of precursor materials utilised. This information would also be used to feed into the Health Economic evaluation studies. The experimental modelling validation will be conducted in collaboration with colleagues at the University of Leeds who have expertise in development of unique 2D and 3D models representative of a range of bone pathologies including osteoporotic bone, metastatic infiltration and multiple myeloma as well as normal bone. The prototype delivery device envisaged will be co-produced by Surgical Innovations (SI) Ltd who specialise in the design and manufacture of creative solutions for minimally invasive surgery (MIS). The experimental modelling work will feed into development of the prototype delivery device, which will be designed to allow for incorporation of the patients autologous stem cells. Health Economic studies will be conducted by the York Health Economics Consortium to fully evaluate the costs and benefits of the technology treatment proposed in comparison with current treatment regimes and resulting healthcare costs from bone fractures. The prototype delivery device produced will be required for follow-on pre-clinical and clinical studies, thus reinforcing the requirement for this device and showing efficacy for use of this device/technology within a clinical setting. Unless positive outcomes from the experimental modelling and validation, prototype delivery device and healthcare economic benefits are achieved from the above designated work packages follow-on clinical studies will not be performed. This MIDOs project also has strong clinical support from the PI and Head of Orthopaedics (Queen's Medical Centre-Nottingham University Hospitals NHS Trust), the Clinical Director of the NIHR Healthcare Technology Co-operative (HTC) in Trauma Management (University Hospitals of Birmingham NHS Foundation Trust) and the Leeds Teaching Hospitals NHS Trust. As such, a PPI (Patient Public Involvement) strategy will also be undertaken involving patients, carers and health care professionals from an early stage to help shape the clinical study and overcome potential barriers to recruitment and uptake. One vitally important outcome of this study will be to evaluate patient opinions on the use of autologous stem cells. This outcome alone will be hugely valuable to many researchers across the world also considering use of autologous stem cells for next generation therapies and treatments. The project recruitment strategy will be discussed with patients aged 50+ from which we will recruit two patients to attend steering group meetings to ensure that the research remains patient centred. Involved patients will also lead on lay dissemination through charities such as the National Osteoporosis Society. Potential numbers and identification of sub-sets of the population to which the above technology could be targeted towards will also be undertaken. This will involve recruitment of patients to complete questionnaires, evaluate usefulness of FRAX and QFracture (online tools to evaluate fracture risk of patients) and to also undergo a non-invasive routine X-ray or CT scan to identify and quantify patients at risk of fracture to compare actual outcomes with above established online tools.

Lay abstract: The research consortium have developed novel tiny biodegradable porous beads (referred to as microspheres) which have huge potential for totally revolutionising the way treatments are administered for osteoporotic patients at risk of bone fracture, whether it is their hip, spine or wrist. These microspheres would provide a novel treatment which would not only repair but could also regenerate new bone tissue. These microspheres would be injected into key areas at high risk of fracture to provide immediate increased bone strength and delivery of growth factors and cells. In addition, there is also huge potential to utilise this technology for applications outside of cardiovascular medicine, for example in oncology and as controlled drug delivery devices. In order to prove and confirm the efficacy of these microspheres as stated above initial pre-clinical (animal) trials followed by clinical trials would need to be conducted, which would be the subject of follow-on studies. However, prior to conducting these pre-clinical and clinical trials alternate studies to warrant and justify the pre-clinical and clinical studies envisaged must be conducted. These studies include i) laboratory experimental modelling utilising synthetic bone models, ii) development of the minimally invasive delivery device which (if successful) would be utilised in the follow-on pre-clinical and clinical trials, iii) a Health Economic Assessment of the novel technology proposed against current treatment regimes and iv) a clinical Patient Public Involvement (PPI) study to evaluate the technology proposed, ascertain patient perception on use of their own stem cells and evaluate population numbers at immediate risk of fracture from osteoporosis. These studies, if successful, would justify and support acquisition of follow-on funds to conduct pre-clinical (animal) and clinical (human) trials for the novel microsphere technology developed.

Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL