The University of Glasgow received a £2.8 million grant in late 2016 in order to develop 3D printed bone for survivors of landmine blasts, which kill roughly 4,300 people each year. The Find a Better Way foundation, which was set up by football legend Sir Bobby Charlton to aid landmine survivors and reduce casualties, awarded the grant, and the researchers have found a way to create bone by 3D printing scaffolds, then coating them with nanolayers of stem cells and a growth factor known as BMP-2 and shaking them up in its Nanokick bioreactor. Earlier this summer, the researchers successfully tested out their 3D printed bone on a dog named Eva. The University of Glasgow researchers have teamed up with other institutions across the UK, including the University of Strathclyde, the University of the West of Scotland (UWS), and the University of Galway, to continue work on the Nanokick bioreactor and the 3D printed bone research – the first time living bone has been grown in a laboratory setting.

The bone is grown by sending nano vibrations across mesenchymal stem cells, found in human bone marrow, which have been suspended in collagen gel. The research began way back in 2009, when the team first put cells onto vibration plates to turn them into bone. While we may not want our 3D printers to vibrate for hours on end, this movement is essential to create the researchers’ 3D printed living bones.

Peter Childs, the co-inventor of the Nanokick bioreactor, explained, “The idea is that the cell membrane ripples at a nanoscale so we are trying to interfere with that process by shaking it.”

The nanokick bioreactor is made of an aluminum block. Piezo actuators, typically used in door bells, are below a plate that conducts precise vibrations and arranged on top of the block. Tissue is magnetically attached to the vibration plate, and when an oscillating voltage passes across the actuators, they expand and contract; doing this at 1,000 hertz actually moves the plate of cells up and down very quickly, causing a nano vibration.

The research team published a paper on their work in the Nature Biomedical Engineering journal. They discovered that tiny vibrations change cells into a 3D model of mineralized bone putty, which is a good outcome, but not as hard as regular human bone would be.

Matthew Dalby, professor of cell engineering at the University of Glasgow and co-inventor of the bioreactor, said, “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.”

The evolution of the nanokick bioreactor.
[Image: Centre for Cell Engineering, Glasgow University]

The team used the nanokicking physics technique, originally created to detect gravitational waves, to make the 3D model. Using the 1,000-hertz vibration frequency, mesenchymal stem cells, which have the potential ability to form cartilage, fat, ligament, and tendons just as well as bone can, are told to specifically form bone.

Surface of bone viewed under a microscope. [Image: BSIP / Getty Images]

“We add the bone putty to an anatomically correct, rigid living scaffold, that we made by 3D printing collagen. 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,” Dalby, also one of the lead authors of the paper, explained. “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. 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.”

The gel that suspends the cells during the nanokicking process is what actually makes the change to bone possible. The cells build up around the collagen, which is the main part of what makes up connective tissue in our bodies. The gels are biocompatible, so surgeons can bridge larger bone gaps using them, and possible rejection can be prevented. Dalby explained that a large scaffold and living cells are what’s needed in order to “heal big defects in bone,” so doctors should be able to replace, or repair, damaged sections of bones using this novel combination of mechanically strong scaffolds and bone putty.

An illustration of the bone growing process.
[Image: Centre for Cell Engineering, Glasgow University]

Dalby said, “All it takes is a few centimetres of bone to extend the length of a leg stump so they can wear a prosthetic.”

“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.”

The nanokick bioreactor is currently being tested for further clinical applications, like ‘switching off’ bone cancer cells, at other laboratories. In 2020, the UK research team’s innovative technique will be tested on humans, when an NHS plastic surgeon will add a little lab-grown bone into a patient’s hand. Then, the research team will attempt to grow the bone putty and add the 3D printed scaffolding within a period of seven days.

[Source: Wired]

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