(55e) Bioinspired Elastin-Based Protein Adhesives

A successful biomedical adhesive must be biocompatible, set in a wet environment, match the mechanical properties of the surrounding tissue, and have proper adhesive and cohesive properties. Current technologies do not meet these needs. We developed bioinspired protein-based adhesives that combine adhesion from DOPA residues found in mussel adhesive proteins with the mechanical properties of elastin, which can also coacervate in response to the environment. Our previous study demonstrated that these proteins are cytocompatible, provide the strongest bonds between aluminum substrates of any rationally designed protein when used completely underwater, and can be easily applied underwater because they coacervate in physiological conditions [1].

In the current study, we examined the adhesion in physiologically relevant environments by using pig skin substrates and curing in a warm, humid environment. We varied the adhesive formulations by adding iron nitrate, tris(hydroxymethyl)phosphine (THP), or sodium periodate and examined different cure times. We evaluated the elastin-based proteins crosslinked with THP and found that the swollen gels were soft and had Young’s moduli that fall within the range of soft tissues (2-200 Pa).

We measured the adhesion strengths of our formulations. Although the adhesion strengths were similar for all the tested concentrations (100, 200, and 300 mg/mL), the variation in adhesion strength was lowest at 200 mg/mL, and we chose this concentration for all other tests. The stoichiometric ratio of crosslinking site to crosslinker was varied, and we found that the ratios that gave the highest adhesion strengths were 3:10 for iron nitrate (15 kPa), 1:50 for THP (18 kPa), and 1:0.1 for sodium periodate (8 kPa). Tisseel, a commercially available sealant, had an adhesion strength of 1.5 kPa. Thus, the two most promising formulations had adhesion strengths ~12-15 times that of Tisseel. We also examined formulations that utilized various crosslinker combinations but did not observe any enhancement in adhesion compared to formulations with an individual crosslinker. Finally, we examined cure times of 10 min, 30 min, 1 h, and 24 h. Both formulations had appreciable adhesion strengths at 10 minutes; however, the formulation with iron nitrate resulted in stable adhesion strengths across the time points.

Overall, the elastin-based protein adhesives showed promise for biomedical applications such as wound closure of soft tissues. Our previous study demonstrated the ability to set in wet environments and the cytocompatibility of the material, and this study now demonstrated that the material can match the stiffness of soft tissues. Furthermore, we used physiologically relevant conditions and found the formulation of iron nitrate at a ratio of 3:10 to be promising due to its high and stable adhesion strengths.

References: [1] Brennan M.J. et al., Biomaterials, 2017; 124: 116-125.