Reducing tissue growth around pacemakers

Materials World magazine
,
6 Jan 2020

A membrane with a special surface structure has proven successful at reducing tissue growth around pacemakers resulting in simpler replacement surgeries. Idha Valeur reports.

Protecting a cardiac pacemaker by reducing tissue growth around the device could become easier due to a new cellulose membrane developed by researchers at ETH Zurich, Switzerland.

The membrane is a hydrogel made of fully hydrated ultra-pure cellulose, produced by a biotech fermentation process. It has the ability to prevent surrounding tissue from attaching to the device, ETH Zurich Scientist, Francesco Robotti, told Materials World.

Coating the pacemaker in a membrane is important as fibrotic tissue growth around the device could complicate surgery when the battery expires and a replacement is needed, which is approximately every five years.

If there is a large amount of fibrotic tissue around the device, the surgeon will have to cut into and remove it. However, this would make the procedure longer and increase the risk of infection, as well as a range of other complications.

Robotti said the technology offers a simple solution to foreign body reaction, a problem he said is under-recognised. He added that more and more patients are going to have implantable devices and the most common battle will be making sure the body does not identify them as foreign, triggering unwanted chronic inflammatory reactions.

‘While we will initially address the implantation of CIEDs [cardiac implantable electronic devices], which are severely affected by foreign body reaction, we are working to optimise our technology to other target implants, where fibrosis and scar tissue formation are not only an issue during device exchange, but can compromise the implant function and cause premature implant failures,’ Robotti said.

Biosynthesised cellulose was chosen to create the membrane due to its superior biocompatibility. ‘Cellulose only minimally elicits the natural inflammatory response that the body mounts against synthetic substrates. Moreover, the human body does not produce the enzyme capable of degrading cellulose – cellulase – and therefore this material is expected to be inert upon implant, providing a long-lasting effect,’ Robotti said.

‘Biosynthesised cellulose has a natural porosity that prevents cell penetration and features a rationally designed surface microstructure that strongly demotes the adhesion and activation of inflammatory cells. Hence, the resulting membrane enforces a separation layer between the target implantable device and the surrounding tissue.’

A structured surface

What makes this new membrane so successful at reducing tissue growth around the pacemaker is its surface structure.

Robotti explained that the surface geometry was designed and optimised especially for its intended purpose. ‘Biosynthesised membranes are designed and manufactured with an isotropic micropattern that interferes with the biological process of cell adhesion. The anti-adhesive surface microstructure enables a unique synergy with the intrinsic properties of biosynthesised cellulose together, ensuring the desired effect of minimising tissue deposition.’

End of year trials

The membrane has already proven successful in the one-year-long animal trials, showing an average reduction of the thickness of the fibrotic tissue of 66% with peaks of 80%. ‘It is important to notice that foreign body reaction intrinsically manifests with very high inter-patient variability. It is therefore essential that a potential solution, such as surface micro engineered biosynthesised cellulose, demotes tissue deposition in those subjects that are prone to the reaction and does not alter the naturally less extreme reaction of other subjects. This is exactly what has been generally observed in the preclinical study,’ Robotti said.

Following animal trials, the team obtained approval from German authorities to initiate the first-in-man clinical trial. At the end of 2019, three hospitals specialising in cardiology and cardiovascular surgery in Germany started enrolling patients with the aim to have the first pacemakers implanted during December 2019. Results on the success of these first devices will be released in early 2020.

Commercial plans

Commercialisation of the membrane has been outsourced to ETH Zurich-spin out company, Hylomorph. Although the patient trials are moving ahead, Robotti admits that it might take a few years for the membrane to be commercially available. ‘With the new European Medical Device Regulation, the whole medical device world is a situation of uncertainty,’ he said. ‘The review and market authorisation process for new devices – as well as re-certification of all existing ones – will proceed slowly and will allow certification in EU only in 2022’.