Adhesive properties and biocompatibility of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate

Adhesives comprising hydrophobically modified gelatin and disuccinimidyl tartrate were prepared with the aim of developing novel tissue adhesives with tissue-penetrating capability and biocompatibility. The hydrophobic groups employed were hexanoyl (Hx; C6), palmitoyl (Pam; C16), stearoyl (Ste; C18), and oleoyl (Ole; C18 unsaturated) groups. The bonding strength of the resulting tissue adhesives against fresh arterial media increased with increasing chain length of the saturated hydrocarbon up to C18 (Ste) when the degree of substitution of hydrocarbons in the hydrophobically modified gelatin molecule was 10% (10Ste) with a fixed succinimidyl group: amino group ratio of 1:1. The 10Ole-disuccinimidyl tartrate adhesive showed slightly lower bonding strength compared with 10Ste-disuccinimidyl tartrate adhesive. In contrast, the use of hydrophobically modified gelatin with a high substitution ratio (50%) showed lower bonding strength compared with the original gelatin. The peeling strength of 10Ste-disuccinimidyl tartrate and 10Ole-disuccinimidyl tartrate adhesives was similar and high compared with other adhesives. Based on the quantitative determination of biocompatibility, using nuclear factor-kappa B/luciferase transgenic mice (BALB/C-Tg (NF-kappa B-RE-luc)-Xen), the level of inflammation associated with 10Ste-disuccinimidyl tartrate adhesive was quite low compared with commercial aldehyde-based adhesive. From these results, 10Ste-disuccinimidyl tartrate adhesive possesses excellent biocompatibility as well as high bonding/peeling strength and, therefore, has potential use in clinical applications.