In Situ Ionically Cross-Linkable Benzaldehyde-Modified Alginate and Its Bilayer Structure as a Tissue Sealant for Dural Closure.

Effective tissue adhesives are vital for surgical applications. We synthesized p-aminobenzaldehyde-modified alginate (AL-ABA) with controlled degrees of substitution (DS, 3.8-13.7%) and cross-linked it ionically using CaCl2. AL-ABA solutions (3 w/v %) gelled rapidly (3-50 s), similar to unmodified alginate. Increasing DS reduced hydrogel stiffness but enhanced dura adhesiveness via Schiff's base formation with tissue amines, reaching 32 kPa at 9% DS. To optimize both adhesion and mechanical integrity, bilayer hydrogels were developed using an AL-ABA primer and AL cover layer, seamlessly bonded by ionic cross-linking. These AL-ABA/AL hydrogels showed strong dural adhesion and high burst pressure resistance (up to 406 mmHg). AL-ABA retained a low cytotoxicity and hemocompatibility. Ionically cross-linked AL-ABA and its bilayer configuration offer promising potential as biocompatible and efficient tissue sealants.