Tissue Adhesives

When a patient has surgery, it is essential that wounds close and heal. Tissue adhesives have become a popular alternative to suturing (stitches) for closing superficial wounds.

Cyanoacrylates are synthetic glues that rapidly polymerise when they contact water or blood. However, some synthetic glues can be toxic to the exposed wound site. Adhesives based on natural proteins such as fibrin offer a potential means of non-toxic wound closure, but the downside is that they have poor mechanical strength.

In Dr. Wang’s group, the team are designing and making adhesives based on natural compounds. Mussels live in a wet, salty environment and need to stick firmly to surfaces. Using their adhesive molecular structures as an inspiration, they have made ‘dendritic’ polymers for use as wet tissue adhesives1

To mimic mussel adhesive proteins (MAPs), a catechol-modified hyperbranched PAE polymer (termed poly(dopamineco-acrylate) or PDA) is made that includes dopamine (a derivative of L-3,4-dihydroxyphenylalanine DOPA, an abundant amino acid in MAPs) and a triacrylate monomer.

The adhesives are delivered in a water-based solution rather than solvent, which can be toxic. The gel forms rapidly on the skin thanks to the heat of the body. The mechanical structures of the adhesives can be fine-tuned by UV light or other cross-linking agents, as the wound requires. The Wang group found fibrinogen to be a very efficient crosslinker, allowing PDA to reach a high adhesion strength (37 KPa) in just 15 minutes, which is substantial for applications such as incisional skin wound closure.

These adhesives will not only function as a closure device and mechanical barrier but also as a local platform for releasing biomolecules, such as genes to promote accelerated wound healing and prevent scar formation. For this reason, the team have designed the adhesive in multiple layers.

The first layer acts as tissue adhesive for wound closure and functions as depot for the controlled release of therapeutic agents, such as genes (figure 1). The top layers (second or third) are designed to strengthen the mechanical properties and provide a flexible water-resistant protective coating. This strategy has been successfully applied on skin incisional wounds and generated a European patent (No. 13153503.1).

They have also developed an adhesive that could be used to treat bone. The team made a hyperbranched poly (beta-amino ester) matrix PDA using curing agents (Fe3+) and reinforcing nano-sized hydroxyapatite particles, and found it to be a safe and efficient adhesive on wet bone2. They anticipate that this adhesive could be used to close the sternum (breastbone) after surgery and the PDA adhesive would biodegrade as the bone heals.

Figure 1: Advanced biodegradable multifunctional dendritic polymer adhesives for topical wound healing.

In Vitro Models: Tissue Adhesives