Bio-inspired polymers in medical adhesion: developments in surgical adhesives for deep tissue bonding

Adhesive technology is rarely applied in orthopaedic medicine. Conventional suturing and tissue stapling remain the standard methods of surgical tissue closure and sealing, despite the technical limitations of suturing in small places and on many types of tissue (such as lung tissue), extended operating times that suturing requires, and significant tissue damage and scarring that stapling can cause. Commercial surgical adhesives exist but are primarily used for stopping bleeding and gluing together skin externally. Deep tissue bonding remains challenging because of the wet and dynamic environment inside the body.

Advancing biomedical glues
In her popular presentation given at Afera’s Annual Conference in Lisbon, Dr. Marleen Kamperman discussed recent developments in biomedical glues. Adhesion systems based on covalent bonding to tissue, hydrophilic (or peg gels) and polyglycerol sebacate acrylates are being advanced by interested groups in academia and many small enterprises. One such company, Paris-based Tissium, formerly Gecko Biomedical, is working on a UV-triggered tissue adhesive. Many others are making surgical adhesives using biomolecules.

Looking at natural adhesive systems
In the aquatic world, several organisms have developed strategies to overcome very similar challenges to the adhesion problems faced by biomedical adhesive developers. Organisms such as the muscle, gecko, velvet worm and caddisfly larvae are able to bond dissimilar materials together (some under seawater) using protein-based adhesives. Dr. Kamperman, who is a professor of polymer science of the Zernike Institute for Advanced Materials at the University in Groningen (NL), established a research group combining her experience in polymer science and materials development with her interest in bio-inspiration stemming from her study of natural systems over the last decade.

Creating fully synthetic polymeric systems
Dr. Kamperman detailed her team’s efforts to mimic the adhesive secretions of marine animals such as the sandcastle worm (Phragmatopoma californica) and the blue muscle (Mytilus edulis) by creating fully synthetic polymeric systems. Characteristic of the proteins found in the adhesive plaque of these 2 organisms is a high proportion of cationic, anionic and catecholic residues (hydroxylated tyrosine, DOPA).

DOPA is involved in a versatile combination of functions: covalent crosslinking, complexation to mineral substrates and bonding to hydrophobic (fouled) surfaces. The anionic and cationic residues are often said to be involved in a secondary interaction that aids cohesion, namely complex coacervation. This is an attractive phase separation of mixtures of polyanions and polycations that results in a highly polyelectrolyte-rich phase in equilibrium with almost pure solvent.

Complex coacervates have very low surface tensions and are water-insoluble, making them highly desirable for underwater adhesives. Additionally, they are mechanically well-suited for adhesion due to their high storage and loss moduli that provide, respectively, bonding strength and dissipation of strain energy.

Dr. Kamperman’s team aims to reproduce the working mechanisms of mussels and sandcastle worms by developing a new class of underwater adhesives based on complex coacervates reinforced with physical interactions. “We are mainly targeting medical applications,” she explained. “We are also interested in marine environments where, for example, we can aid in growing seaweed or oysters.”

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