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

Abstract

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.

Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast‐Relaxing Boronate Hydrogels

“…[35] McKinnon et al demonstrated that CANs can be designed with controlled elastic moduli and stress relaxation time constants while being cytocompatible for myoblast encapsulation. [36] Boronate crosslinks between a boronic acid and diol have shown many potential applications for glucose sensor, drug delivery, and self-healing materials, [37][38][39][40] although limited applications were achieved for stable cell culture scaffolds. [37,41] Tang et al developed covalent adaptable poly(ethylene glycol) hydrogels by screening boronate crosslinks formed by a range of different boronic acids and diols to achieve tunable rates of stress relaxation.…”

Advances in the Fabrication of Biomaterials for Gradient Tissue Engineering

“…For instance, cellularized osteochondral scaffolds have been prepared by using a small amount of solvent glue to bind different polymeric scaffolds [23]. Glues such as alginateboronic acid have been developed to bind pre-cast hydrogels, such as agarose, acrylamide, and chitosan-catechol [24]. In these cases, however, the attractive interactions within each material layer Peer reviewed version of the manuscript published in final form in Trends in Biotechnology (2020).…”

Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells

“…The reaction between boric acid and diol compounds could produce dynamic boronate bonds, which are common in biofilms of bacteria that combine carbohydrates with lectin. Phenylboronic acid (PBA), also called “synthetic lectin”, was applied to mimic chemical structure of lectins in bacteria and obtain self-healing materials [ 103 ]. However, its primary/secondary amines are toxic, and PBA needs to be modified to a polymer backbone at a pH lower than the physiological environment.…”