Effects of phenolic hydroxyl group structures of Alaska pollock gelatin-based adhesives on soft tissue adhesion and biocompatibility

Marine mussels adhere to various types of substrates in aqueous/wet environments, and their adhesion is controlled by the catechol structure of the phenolic hydroxyl groups. Tissue adhesives with a catechol structure have been designed based on this biomimetic adhesion mechanism. However, the effects of the chemical structure of the phenolic hydroxyl groups on tissue adhesion and biocompatibility have not yet been systematically investigated. In this study, various phenolic hydroxyl group-modified Alaska pollock gelatins (nHy-ApGltns (n = 0, 1, 2, 3)) were synthesized and their function as tissue adhesives with a poly(ethylene glycol)-based 4-armed crosslinker (4S-PEG) was evaluated. The nHy-ApGltn adhesives showed increases in bulk strength and decreases in swelling compared to the original-ApGltn (Org-ApGltn) adhesive. The tensile stress and Young's modulus of the nHy-ApGltn adhesives increased with the introduction of nHy groups. The burst strength of the nHy-ApGltn adhesives had a maximum value at each content; however, a high content of nHy in the nHy-ApGltn adhesives had a negative effect on the burst strength. The burst strength of the porcine aorta with all the nHy-ApGltn adhesives was higher than that with human blood pressure. From histological observations after burst strength measurements, the 2Hy- and 3Hy-ApGltn adhesives showed stable interfacial adhesion compared to the Org-, 0Hy-, and 1Hy-ApGltn adhesives. The nHy-ApGltn (n = 0, 3) adhesives implanted subcutaneously in rats completely degraded within 64 days without severe inflammation or foreign body reactions. Therefore, nHy-ApGltn adhesives with low nHy content have excellent tissue adhesion and biocompatibility in wet environments and have the potential for use in biomedical applications.