Impact case study database

Trauma or disease requiring bone to be replaced can be grafted by surgeons. In fact, in the US alone, there are over 500,000 spinal fusion surgeries requiring a bone graft substitute every year. However, commercial synthetic bone graft substitutes have been typically synthesised using either ceramic-based approaches or melt-derived glass approaches. These traditional materials are dense, unlike bone mineral, and have had limited clinical success both due to generation of fibrous tissue growth around the material, rather than new bone, and lack of resorption into the body. These failures account for around 20% of cases, leading to significant implications on patient health, quality of life and ability to return to work, with concomitant socio-economic costs to society. Even with these limitations, the current annual share for synthetic substitutes represents almost a third of the USD3.2 billion bone graft global market. Research started in 2005 at the University of Aberdeen – supported first by an EPSRC Advanced Research Fellowship awarded to Professor Iain Gibson ( P1) and then a Scottish Enterprise Proof of Concept Grant ( P2) – sought to address this problem by developing a novel synthetic bone graft substitute using a different approach to synthesise the materials. This multi-disciplinary research project was carried out within the Institute of Medical Sciences and the Department of Chemistry (with co-applicants Skakle and Aspden), and included pre-clinical assessment managed through sub-contracted collaborators.

The research aimed to develop a synthetic approach that produced a bone graft scaffold material that exhibited chemical and morphological similarities to bone mineral, based on the hypothesis that such a scaffold architecture would support faster bone repair and be capable of cell-mediated resorption. If successful this would address two unmet clinical needs: an off-the-shelf synthetic bone graft substitute that would perform as well as or better than autograft (the clinical gold standard, but an approach that is accompanied by longer patient healing time, and postoperative pain at the autograft harvest site); and a synthetic material that would eventually be fully remodelled and replaced by host bone.

The research involved the development of both a novel composition of silicate-containing calcium phosphate material and the process of making it into a new synthetic bone graft substitute material. [ R1, R2] The resulting material was designed to have a crystal morphology and size that is closer to that of the bone mineral crystals in bone, compared to other synthetic bone graft materials, with crystal dimensions ranging from approximately 50 nm to 150 nm. The processing of the composition into a granule bone graft resulted in a similar amount of total porosity to common macroporous bone grafts (>75% total porosity), but the size of the pores is significantly smaller (sub-micron sized), rather than macropores (100-500 microns), meaning that the resulting material has a high surface area. The hypothesis of this material design was that making a bone graft with much smaller crystal sizes and a high surface area would result in a bone graft that would provide a surface that supports bone repair and would be more readily remodelled than current ‘ceramic’ synthetic bone graft substitutes. Further research identified specific microstructural features in calcium phosphate materials, and methods to produce these, that led to an osteoinductive property in the material [ R3]. Pre-clinical testing of this material showed that the rate of bone formation was significantly faster than observed for one of the leading synthetic bone graft substitutes on the market, using a challenging model of spinal fusion. This study also showed that the graft material was remodelled and slowly replaced by host bone.

Following the completion of the Proof-of-Concept project, the technology and intellectual property formed the basis of a spin-out company from the University of Aberdeen in 2011 (SIRAKOSS Ltd.), who continue to commercialise the technology.

Research and development of the underpinning research continued through a Royal Commission for the Exhibition of 1851 Industrial Fellowship funded PhD project at the University of Aberdeen, supervised by Professor Iain Gibson from 2013 to 2016.

Building on the underpinning research, a recent study by SIRAKOSS demonstrated the efficacy and safety of the final developed product in a regulatory pre-clinical study, leading to 100% fusion success after 26 weeks, which further validated the Aberdeen-led research [ R4].