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Biomaterials which can repair injuries

An implant for major skull injuries is one of the results of almost ten years of collaboration between the teams lead by materials expert Håkan Engqvist and polymer chemist Jöns Hilborn.

One is an expert in ceramic bone implants, the other a specialist in the interaction between polymers and human body cells. Together they are developing and improving the orthopaedic and dental biomaterials of the future.

Light floods into the cell laboratory of the Ångström Laboratory clean room. Here, research teams work side by side and together, often crossing disciplinary boundaries. The collaboration between materials expert Håkan Engqvist’s team and polymer chemist Jöns Hilborn’s team has lasted almost ten years.

“Our work is very interlinked with many shared projects and courses,” says Håkan Engqvist, professor of Applied Materials Science. “When you have worked together for so long, it doesn’t take long before one of my or John’s researchers understands what problem we are trying to solve.”

In his hand he is holding one of the results of this collaboration, an implant for major skull injuries. It looks like a beautiful mosaic with a neat precise pattern. The ceramic is a Håkan Engqvist team speciality.

“The ceramic is made from two calcium phosphate salts which we mix into a cement paste. We then mould it onto a titanium metal mesh. We 3D print both the mesh and the mould based on the patient’s CT image.”

Giving the ceramic material the right properties is not just about the biology but also mechanics, says Håkan Engqvist.

“The plate must be shock resistant. In order to make it as strong as possible, you have to vary the grain size of the salts and their chemical composition and how much water or other fluid you need to mix in to make the paste. This means that a great many parameters need to be tested.”

Another factor which can also help to strengthen ceramic plates is plaster or other materials based on synthetic polymers. In order to understand how their properties can be best applied to their purpose and will not be rejected by the body, professor Jöns Hilborn’s team analyse the response of cells and tissues at molecular level. Into materials which might be used for implants, researchers add molecules made up of polymers. On the surface of the material, selected cells are planted and the reactions are examined.

“The results we obtain are very likely to be the same as if the material was implanted into something living,” says Jöns Hilborn. He adds:

“Even more interesting are the body’s own polymers which are also able to control biological functions. We have observed that when the body’s natural substance hyaluronic acid is added to the implant material, the surrounding blood vessels grow better.”

Studies have shown that some gels injected into animal tissue give protection against inflammation, hasten the healing of wounds and reduce scarring.

“Injectable gels also work very well to form bone or cartilage. One of the researchers in my lab has developed a gel containing a substance intended to search for bones needing treatment for osteoporosis. So what would be interesting with regard to bone generation the ability to produce injectable ceramic composites. Håkan and I want to do further research into this.”

Another advantage of the ceramic material is that its composition prevents the surrounding skin from becoming thinner. Thin skin may suffer from splitting and pitting. In addition, Håkan Engqvist’s research team has published two articles describing how the material triggers bone formation in the head.

“This is feedback we have received from the doctors we work with who have regularly followed up their patients’ progress over several years. The first patient has now had his ceramic implant for over five years. It can be seen that bone is being formed more and more densely around the implant. This also leads to many exciting thoughts about how you can build up bone,” says Håkan Engqvist.

The idea of using a mosaic to repair bone comes from plastic and reconstructive surgeon Thomas Engstrand at Karolinska Institutet. His collaboration with the researchers at the Ångström Laboratory is  now in its fifth year.

“We also carry out research in close collaboration with orthopaedic practitioners and radiologists. We aim to produce new biomaterials which can be used in several different parts of the body. We can already tailor-make various kinds of implant, other interesting areas we are looking into are the back and the face.”

One example is fractured vertebrae. These have to be stabilised so that they do not cause severe pain. Håkan Engqvist’s team have created a new technique using a ready-mixed ceramic material which can be injected into the site of the injury to stiffen the fracture. A simple and time-saving method which, however, is a long way from being used clinically.

“Much documentation will be required to take it further, as well as many strength tests in order to make the material and evaluate it – firstly in cells and then in animals. The whole chain of evaluation has to work from pre-clinical to clinical to commercialisation via a company,” says Håkan Engqvist.

“A completely new material configured in a new way and which has never been tested on humans would take many years before it became reality. But the work we do in our cell lab involves salts which are already used in many different forms in humans. There is a lot to fall back upon. Most of what  we do is effects studies: If I mix these salts in a clever way, can I achieve a better effect than at present?”

26 April 2016