A new avenue for synthetic bone grafts

2 October 2017

Bone grafts are the second most commonly transplanted tissue after blood transfusions. The use of synthetic bone graft substitutes is increasing, but the challenge is to make them as ‘clever’ as their natural counterparts in stimulating fusion with the host bone. Bristol researchers believe a tiny lipid molecule could provide the answer.

Use of bone grafts is widespread in orthopaedic surgery. The standard method involves harvesting the patient’s own bone (known as autogenous grafts). However, this is not always possible and it can pose extra risk to the patient, hence the development of synthetic bone graft substitutes.

There’s a drawback, however; synthetic grafts frequently lack the biological properties of autogenous grafts that stimulate the patient’s cells to form new bone and that help the graft to fuse with the host tissue. This means that there’s a greater chance that the implant will loosen and eventually fail.

To try to overcome this, biomaterials researchers have experimented with biological agents such as peptides and proteins, which they apply as a coating to synthetic grafts. But these materials are costly and often unable to withstand the sterilisation and handling processes needed for clinical use.

Dr Jason Mansell (University of the West of England) and Professor Ashley Blom (University of Bristol) have been exploring whether a small lipid molecule, FHBP, could provide a viable alternative. FHBP has been shown to enhance the formation and maturation of mature bone-forming cells (osteoblasts) in combination with active vitamin D3. Dr. Jason Mansell and Professor Ashley Blom are studying the potential of FHBP to improve the biological action of synthetic bone grafts.

An EBI Clinical Primer Scheme was a chance for Dr Gráinne Neary, an equine veterinarian, to join the project and gain experience of high-level research alongside her advanced clinical training. As an undergraduate student, Gráinne had been awarded funding to undertake research relating to diseases of sheep and horses at the University of Cambridge and the University College of Dublin respectively. She was interested in following up this early career research experience with a project that was relevant to both human and animal health, and the EBI primer scheme provided the opportunity to do this.

In collaboration with Dr Mansell and Professor Blom, Dr Neary found an opportunity to build on these foundations with the idea of pursuing a research-oriented career. The project involved coating ceramic (hydroxyapatite) bone grafts with FHBP to see if this could accelerate the maturation of immature bone-forming cells (stromal cells) into osteoblasts on the bone graft surface. The researchers tested the FHBP modified grafts in human and sheep bone cell cultures spiked with active vitamin D3 and compared their performance with that of unmodified grafts.

The study showed that coating the grafts with FHBP did indeed speed up maturation of bone-forming cells on the bone graft surface. However, the difference in responses between sheep and human cell cultures made sheep an unsuitable animal model without further investigations. Once further work is complete, the researchers will submit a paper to the journal Acta Biomaterialia.

In realizing the exciting potential of this work Dr Mansell and Professor Blom continue to collaborate in finding novel ways to improve the biocompatibility of implantable materials. Dr Neary has since been awarded a Wellcome Trust-funded fellowship at the University of Edinburgh allowing her to combine a clinical and research career.

Dr Neary said: ‘The EBI Clinical Primer Scheme gave me an excellent opportunity to engage in clinical research in an internationally competitive environment. It made me more aware of the opportunities available to combine high-level research with advanced clinical training, which inspired me to seek a career where I can effectively combine the two. I found the Clinical Primer experience extremely rewarding as it allowed me to build on my knowledge of laboratory research, scientific writing and grant applications. I now feel more prepared to embrace the world of research in a challenging academic environment.

‘I worked closely with the University’s Functional Neurosurgery Group at Southmead Hospital while conducting my own orthopaedic research. This gave me insight into areas of research I was previously unfamiliar with. I would encourage other EBI Clinical Primer Scheme candidates to get involved in groups outside their own to broaden their research experience.’