Cerebral cure

Searching for a safer, more efficient alternative to today’s imprecise, time-intensive methods for treating cerebral aneurysms, a group of University-Wisconsin-Madison biomedical engineers and physicians has developed a system that not only shaves hours from the current procedure time, but also plays an active role in healing the area.

Essentially, a cerebral aneurysm is a 'balloon' or bulge that forms along a weak wall of an artery or vein in the brain; about 40 per cent of patients whose aneurysm ruptures die within 24 hours.

All cerebral aneurysms have the potential to rupture and cause bleeding within the brain — though most go unnoticed until they rupture or are detected on brain images for another condition.

Coil embolisation is one common method for treating a cerebral aneurysm. The process requires surgeons to feed wire coils into the bulged-out area via a catheter until the aneurysm is full and the coil 'ball' blocks blood flow to the aneurysm.

'The hope is that this bundle of wire is going to instigate a wound-healing response or scar formation around the aneurysm that will wall this part off from the blood vessel and no longer have a risk of rupture,' said Assistant Prof Kristyn Masters.

However, she said, the process can take up to eight hours and, because blood flowing past the coils could put even more pressure on the aneurysm, it actually may increase the risk of rupture.

Neurosurgery resident Roham Moftakhar had an idea for an alternative device. So he recruited Biomedical Engineering and Engineering Physics Associate Prof Wendy Crone and Masters to the project because of their expertise, respectively, in shape-memory metals and biomaterials.

Together, they devised a method that strips the process down to a catheter, a single wire coil, and an expandable 'balloon' — a bioactive polymer shell.

'Probably one of the most important things to our surgeon is that this only involves putting in a single coil,' said Masters. 'It could dramatically — by orders of magnitude — decrease the time to occlude these aneurysms.'

For the wire coil, the group chose nickel-titanium, a shape-memory alloy already in use for aneurysm treatment. When the wire is cool — somewhat below body temperature — it straightens easily and users can thread it into a tiny catheter. Inserted into the body via the catheter, the wire warms. At body temperature, it wants to coil, but the catheter keeps the wire straight until it reaches its target. 'This coil, as it’s exiting from the catheter, expands the balloon to then create instant contact with the surrounding aneurysm shell,' said Masters.

Rather than choose just a biocompatible material for the balloon, the group decided to use a bioactive material to stimulate and accelerate healing. But the researchers’ list of required material properties was long: it had to be biocompatible, haemocompatible, highly elastic, able to be made into thin films or capsules, and, ideally, contain elements that promote wound healing. 'When we started thinking about this, we realised there wasn’t a good existing material to meet these criteria,' said Masters.

So Masters engineered one. She began with polyurethane, an elastic biocompatible polymer widely used in medical devices. To make the material hemocompatible, she incorporated varying amounts of hyaluronic acid, an antithrombotic molecule — or, an anti-coagulant — that stimulates wound healing.

'We found that even at our lowest hyaluronic acid incorporation, we get complete elimination of platelet adhesion to the materials, so these are highly hemocompatible,' she said. 'The resulting polyurethane hyaluronic acid copolymer also has 1,500 per cent elongation, perfect for making it into thin films for the balloon.' The researchers currently are testing their system in in vitro aneurysm models they constructed from silicone.

Although she tailored the new hemocompatible material for the group’s aneurysm occlusion device, Masters is excited about the potential polyurethane hyaluronic acid copolymers have in applications like using native biomolecules to deliver bioactivity. As a result, she has spun off several additional research projects.

'You can really tailor the physical and biological properties on your materials based on how much of the hyaluronic acid you put in them,' she said.