Rapidly Cross-Linkable DOPA Containing Terpolymer Adhesives and PEG-Based Cross-Linkers for Biomedical Applications

A new three-component bio-inspired adhesive was synthesized that is a terpolymer composed of a water-soluble segment, an interfacial adhesion segment, and a cross-linking segment. Strong wet adhesion properties are obtained utilizing a 3,4-dihydroxy-l-phenylalanine (DOPA) moiety. Poly­(acrylic acid) provides high water solubility due to strong ionic interactions with water. An acrylic acid N-hydroxysuccinimide ester (NHS) was included in the adhesive polymer to allow rapid cross-linking with thiol-terminated, 3-armed poly­(ethylene glycol) cross-linking agents. The thiol terminal poly­(ethylene glycol) was designed to be bulky to avoid possible penetration of molecules to the cell and tissue. The NHS and thiol groups react within 30 s to form covalent bonds. This design allows for rapid optimization of properties for specific applications. Lap shear strength tests on wet porcine skin demonstrated a 190% increased value in adhesion strength for adhesives having the DOPA moiety. After cross-linking, adhesion was enhanced by 450% over poly­(acrylic acid-co-acrylic acid NHS) and was 240% higher than un-cross-linked poly­(acrylic acid-co-acrylic acid NHS-co-N-methacryloyl-3,4-dihydroxyl-l-phenylalanine). Rheology studies show adhesive viscosity drops significantly at high shear rates, demonstrating its potential to be injected via syringe. The cross-linked adhesive displayed much stronger mechanical properties and higher elastic and viscous moduli than an un-cross-linked adhesive model. Furthermore, the cross-linked adhesive has enhanced moduli near body temperature (38 °C) as compared to room temperature (23 °C), increasing the applications as a biomedical adhesive.