Alginate-Boronic Acid: pH-Triggered Bioinspired Glue for Hydrogel Assembly

The development of bioadhesives has become an emerging research field for tissue sealants, wound dressings, and hemostatic agents. However, assembling hydrogels using bioadhesive-mediated attachment remains a challenging task. Significantly high water content (>90%) in hydrogels compared to that of biological tissues is the main cause of failure. Considering that hydrogels are primary testing scaffolds mimicking in vivo environments, developing strategies to assemble hydrogels that exhibit diverse properties is important. Self-healing gels have been reported, but such gels often lack biocompatibility, and two gel pieces should be identical in chemistry for assembly, thus not allowing co-existence of diverse biological environments. Herein, a mussel-mimetic cis-diol-based adhesive, alginate-boronic acid, that exhibits pH-responsive curing from a viscoelastic solution to soft gels is developed. Associated mechanisms are that 1) polymeric diffusion occurs at interfaces utilizing intrinsic high water content; 2) the conjugated cis-diols strongly interact/entangle with hydrogel chains; 3) curing processes begin by a slight increase in pH, resulting in robust attachment of diverse types of hydrogel building blocks for assembly. The findings obtained with alginate-boronic acid glues suggest a rational design principle to attach diverse hydrogel building blocks to provide platforms mimicking in vivo environments.