Protein-based adhesives hold great promise as biomedical adhesives (bioadhesives) due to their exceptional biocompatibility and biodegradability. However, their wet adhesion abilities remain a significant challenge. Marine adhesive proteins (MAPs), a class of proteins renowned for their superior underwater adhesion abilities, provide critical inspiration for the design of robust protein-based bioadhesives. Herein, inspired by the adhesion mechanisms of sandcastle worms and barnacles, a novel fusion protein termed E110B was genetically engineered by combining a phase-transition elastin-like polypeptide (ELP) with the self-assembling barnacle 19 kDa cement protein (cp19k), an adhesive protein capable of nonspecifically adhering to various substrates. It was demonstrated that E110B can undergo temperature-dependent reversible phase transition, enabling convenient and scalable purification of recombinant proteins through a nonchromatographic method. Moreover, E110B was able to self-assemble into ordered supramolecular nanofibers, probably facilitated by the β-sheet structure of the cp19k module. Both phase transition and self-assembly significantly enhanced the adhesive strength of E110B. As a result, the self-assembled and phase-transitioned E110B-based adhesive demonstrated robust adhesion, with a maximum adhesion strength surpassing 4.5 MPa on glass and steel substrates under ambient conditions, outperforming all previously reported recombinant barnacle cement protein-based adhesives. Even in high-moisture environments (>90% relative humidity), the adhesive maintained a high adhesion strength of 0.31 ± 0.03 MPa. In addition to its robust adhesion, E110B achieved a comparable yield to other recombinant cp19k counterparts and exhibited good biocompatibility. These attributes make the E110B-based adhesive suitable for coating metallic and ceramic medical implants to improve their biocompatibility and biofunctionality. In summary, this study underscores the potential of combining ELPs with MAPs for designing scalable, thermoresponsive, and robust protein-based bioadhesives, opening a new avenue toward the development of advanced bioadhesives.
Keywords: barnacle cp19k; bioadhesives; elastin-like polypeptides; phase transition; self-assembly.