Scientists have grown living bone in the laboratory for the first time – and it could help bomb blast victims.
A team from the Universities of Glasgow, Strathclyde, the West of Scotland and Galway have created a device that sends nano vibrations across mesenchymal stem cells suspended in a collagen gel.
The authors of the paper, published in the Nature Biomedical Engineering journal, found that these tiny vibrations turn the cells into a 3D model of mineralised bone 'putty'. This putty isn't quite as hard as bone at this stage. That's where the body comes in.
"We add the bone putty to an anatomically correct, rigid living scaffold, that we made by 3D printing collagen," says Matthew Dalby, professor of cell engineering at the University of Glasgow, and one of the lead authors of the paper. "We put lots of cells in the body so it has a chance to integrate this new bone. We tell the cells what to do in the lab, then the body can act as a bioreactor to do the rest."
The team began the research back in 2009, placing cells onto vibration plates and watching them turn into bone. "The challenge with making bone in the lab which can then be used in a patient is that it needs to be 3D, viable and cellular," he says.
To make this 3D model, they turned to physics.
‘Nanokicking’ is a biological technique that borrowed tools from gravitational wave research. The team collaborated with physicists who had built equipment to measure these waves.
"We were supplying the cells with vibrations of 20 nanometers – for gravity waves that's huge, but their kit is more than sensitive enough to do it," says Dalby. "We take the cells out of a patient, pop them into a gel and put them into a bioreactor, called the nanokick, which vibrates the cells at about 1,000 times a second."
Mesenchymal stem cells, which are found in human bone marrow, have the potential to form cartilage, ligament, tendons and fat as well as bone. This 1,000-hertz vibration frequency tells the cells to form bone specifically.
The gel it is suspended in is what allows the bone to become 3D – the cells can build around the collagen, which is the main component of connective tissue in the human body. This means the gels are bio–compatible with us, preventing the problem of rejection and letting surgeons bridge larger gaps in bone.
Surgeons currently use bone grafts from the pelvis to fix broken bones. They can only take a couple of teaspoons of living graft. They must then use an allograft – a sample taken from another person, with the living cells removed – as a scaffold. Using material from another person increases the chances the body will reject the graft.
"To heal big defects in bone, you need living cells and a large scaffold. That's what we are trying to do," Dalby says. This combination of bone putty and mechanically strong scaffolds could repair or replace damaged sections of bone caused by osteoporosis.
Dalby speaks with earnest about how it can also help civilian and solider blast injuries, once it is established within the NHS. "All it takes is a few centimetres of bone to extend the length of a leg stump so they can wear a prosthetic," he explains.
"We are getting better at surviving but we have a lot of trauma injuries. In partnership with Sir Bobby Charlton’s landmine charity Find A Better Way, we have already proven the effectiveness of our scaffolds in veterinary medicine, by helping to grow new bone to save the leg of a dog who would otherwise have had to have it amputated."
"The NHS has the governance and rigid procedures to make sure our tech is rolled out correctly first, before we take it to developing countries," Dalby says.
Find a Better Way, which funds this research, helps individuals and communities heal from the devastating impact of landmines and other explosive remnants of war.
Peter Childs co-invented the nanokick bioreactor, which he says is the result a few failed designs. "The idea is that the cell membrane ripples at a nanoscale so we are trying to interfere with that process by shaking it," he explains further.
The nanokick bioreactor is made of an aluminium block with piezo actuators arranged on top, which sit below a plate that conducts very precise vibrations. The tissue itself is magnetically attached to that moving plate. The piezo actuators, which are typically used in door bells, expand and contract when you pass an oscillating (rhythmical) voltage across them. If you do that at 1,000 hertz, you move the plate of cells up and down so quickly that it causes a vibration. The nano vibrations can change the regulation of ion channels, for example, causing a calcium or potassium influx.
This technique will be tested on humans in 2020, when an NHS plastic surgeon will deliver a small bit of lab-grown bone into a patient's hand. Once this is in motion, Dalby says, the team will work towards growing the bone putty and adding the scaffolding within a week.
The nanokick bioreactor has been sent off to other laboratories, to test further clinical applications. For example, one laboratory is in the preliminary stages of using it to 'switch off' bone cancer cells.
This article was originally published by WIRED UK
