What do gravitational waves and bone grafting have in common?

It turns out that the hunt for one could transform the way we carry out the other.

What if you could grow a bone in the lab using the power of vibration? It sounds fantastic, but researchers from the University of the West of Scotland (UWS) and the University of Glasgow (UoG) have collaborated on a method which could do exactly that.

Bone is the second most commonly transplanted tissue in the world. Unfortunately, bone grafting surgery is a rather painful and complicated procedure which sees bone samples removed from other parts of a patient’s body before being encouraged to grow or fuse with other bones — usually through the use of bone-forming chemicals or growth factors. Potential complications include the risk of rejection and even tumours.

Back in 2010, stem cell engineers at the University of Glasgow were interested in the effect vibrations had on multipotent stem cells — that is, cells which can grow into many types of tissue needed throughout the body such as fat, cartilage and bone. They realised that physical stimulation might trigger bone growth, as bones are very responsive to pressure — indeed, it is the stress placed on them from movement, called ‘bone loading’, that keeps bones repairing themselves.

It turns out that shaking stem cells by billionths of a metre — or nanometres — flicks on switches which turn these cells into bone-producing cells, triggering the transformation that happens naturally as the bones in our body grow and heal throughout our lifetime. As noted by UWS researcher Professor Stuart Reid, “The scale of movement that triggers the cells to transform is so small it would be the same as sliding a single sheet of paper in and out from under a football on a table.”

To measure movements this small, the team used the same laser technology as in the hunt for gravitational waves, albeit scaled down. UoG Professor Matt Dalby explained, “A colleague of mine… started collaborating with gravity wave physicists [at UWS], who developed all these techniques for making very small measurements as they wanted to detect gravity waves, which are incredibly small — much more than our ‘nanokicks’.”

Christina Boyle, a PhD student at UWS, explained that her group developed nanokick bioreactors to perform different types of experiments on different types of cells, controlling factors such as “the height of the nanovibration, the amplitude, the number of times we shake the cells per second, the frequency and the overall duration of stimulation”.

“After the stimulation period, we take the cells for analysis to see how they reacted to the nanokicking,” Boyle continued. “We can then further analyse these by looking at the cells down a microscope to see how their shape has changed, or even look even deeper into their genes to see which ones have been switched on or switched off.”

Professor Dalby said it seemed like “a mad, eccentric idea… but as we vibrate the stem cells, we tell them to turn into bone cells, and we can envisage clinical use for that in bone augmentation processes”.

“It’s amazing that technology developed to look for gravitational waves has a down-to-earth application in revolutionising bone treatments for cleaner, safer and more effective therapy,” he said.

So exactly how would these cells be implemented in bone grafting surgery? Professor Reid explained that the technique could allow scientists to grow new pieces of bone from a patient’s own stem cells, either from their bone marrow or even from fat cells from liposuction. The nanokicked bone could then be implanted where needed to fuse with existing bone and heal bone damage or fractures.

“By using a frame, we can design bespoke grafts replicating the area of need in the patient,” Professor Reid said.

“And by using stem cells harvested from each patient, this process would reduce the risk of rejection. This could mean the end of the painful practice of taking grafts from the patient’s own hip, for example, revolutionising patient care.”

Nanokicking could also have an important role in drug discovery and has shown promise in other areas of research, such as osteoporosis. Early results suggest that the technology could be used to identify therapeutics which slow down fast-growing bone cancers.

“Perhaps best of all, though, this could help us develop new treatments and drugs for bone disease, something which has proved very difficult to combat in the past,” said Professor Reid.

The nanokicking research is funded by the Engineering and Physical Sciences Research Council (EPSRC) and Biotechnology and Biological Sciences Research Council (BBSRC). The funding has enabled the research team to scale up the bioreactor, to make bioreactor dedicated consumables and to improve the quality of the bone graft produced.

With the research still at the validation stage, said Professor Dalby, the researchers’ next step is to understand how their living bone graft compares to synthetic, non-living alternatives, before making their way through the regulatory process. The team aim to test the bone in people within 3–5 years, with the potential for therapy to be available in 10 years.

Further down the line, the researchers may even be possible to nanokick patients directly to heal fractures without surgery. They are also commercialising the bioreactor they have designed to make it available to other scientists and bone researchers.

“We hope that this research can lead to an off-the-shelf solution to demand for living bone graft,” said Professor Dalby. “This demand might be within the NHS to deal with both elective and trauma surgeries, but could also be worldwide to supply high-quality bone graft to hard-to-reach places.

“Further, we are developing acoustic nanokicking and, while this is in very early-stage development, we hope this will be used to apply nanokicking directly to patients to help bone healing.

“Nanokicking offers tremendous potential and we have only just scratched the surface on what this process enables us to do.”

The technology was featured at this year’s Royal Society Summer Science Exhibition as one of 22 exhibits, selected via a competitive process, of cutting-edge science and research being done right now across the UK. The research was also published in the July 2016 edition of the Journal of Biomedical Nanotechnology.