Bridging polymer chains create strong tissue adhesive

Tissue adhesives are a less invasive method than sutures and staples for closing wounds and stemming bleeding. Complex coacervates – a mixture of positively and negatively charged polymers in an aqueous solution – have recently emerged as promising candidates for tissue adhesives, given their ability to bond readily to wet surfaces. Yet these materials, too, struggle to remain adhered to underlying soft tissues when those tissues deform.

Researchers at the University of Groningen have now designed a complex coacervate adhesive, composed of poly(allylamine hydrochloride) (pAH) and polysulphopropyl methacrylate (pSPMA), that proves more robust against biological tissue deformation. By pre-coating the tissue with pAH, the adhesive forms a polymer-rich bridging layer in contact with the tissue. Chemist Marleen Kamperman of the University of Groningen, who led the research, explains: ‘We have created a sticky gel held together by electrostatic interactions. What is elegant about this material is that its bonding strength can be modified very precisely by adjusting the salt concentration. At a high salt content, a liquid material forms that is easy to inject or apply, and which subsequently hardens as the salt concentration decreases.’

Salt switch

Complex coacervates have a low surface tension with water, which makes them an effective adhesive under wet conditions. Furthermore, their tuneable mechanical properties make them suitable for use on a variety of tissues and materials, including skin, bone, and synthetic implants. ‘When you introduce the coacervate adhesive into a moist environment, the material undergoes what is known as a salt switch,’ explains lead author and biologist Ayla Kwant. ‘During this process, salt diffuses out of the adhesive and into the underlying tissue, causing the adhesive to harden.’

Tissue adhesives require substantial adhesion to remain bonded to continuously moving tissues, such as the heart, lungs, and muscles. ‘We have been working on coacervate adhesives for some time and are well acquainted with the conditions required to create strong adhesion,’ says Kamperman. ‘We therefore began this research with a list of desired properties and set about identifying the appropriate polymers to match them.’

Fairly early in the research, Kwant discovered that pAH and pSPMA together formed a coacervate adhesive with strong bonding properties. ‘We then came across an earlier publication showing that bridging polymers, through self-association of electrostatic interactions, improved adhesion between hydrogels and tissues,’ says Kwant. ‘At that point, we wanted to test whether this would hold true for our coacervate adhesive as well.’

Dark rooms

To investigate this, Kwant first determined the adhesive strength of the coacervate adhesive itself by pulling it apart using a rheometer. She then bonded hydrogel or tissue substrates together with the coacervate adhesive and pulled them apart vertically using a tensile tester, an instrument that measures tensile strength. ‘By pre-coating some of these substrates with the pAH polymers, I was able to compare the adhesive strength between substrates with and without bridging polymers,’ says Kwant. ‘The results clearly showed that those which had been pre-coated adhered more strongly.’

Kwant then wanted to visualise the penetration depth of the bridging polymers into the hydrogels and tissues – which proved to be one of the greatest challenges of the research. ‘To examine the depth, I tested various microscopes and spent a long time searching for the right settings,’ Kwant explains. ‘I spent many hours in dark rooms to get it right.’

Degradation

As a next step, Kamperman wants to select a specific application for the coacervate adhesive in order to optimise it in a targeted manner. ‘We have strong collaborations with the University Medical Centre Groningen, which is already a step towards a concrete application,’ says Kamperman. ‘But before the adhesive can be deployed more broadly, a great deal of clinical testing still needs to be carried out. This is a long-term endeavour.’

The researchers also intend to test how the coacervate adhesive behaves inside the body and how quickly it degrades. Kwant is currently focusing on the biologically related work: ‘I am now conducting a great many in vitro experiments with the adhesive on various cell lines. Step by step, we aim to progress towards a more realistic model in which the adhesive can be tested.’

Ayla Kwant, et al., Improving complex coacervate tissue adhesive performance using bridging polymer chains, Biomacromolecules (2025), doi:10.1021/acs.biomac.4c01801