A Comparative Review of Phenylboronic Acid-Functionalized Hydrogels as Glucose-Responsive Biomaterials: Design Chemistry, Characterization and Biological Behaviour
DOI:
https://doi.org/10.64354/pabyck07Keywords:
phenylboronic acid; glucose-responsive hydrogel; boronate ester; dynamic covalent chemistry; self-regulated insulin delivery; biocompatibility; diabetic wound healingAbstract
Phenylboronic acid (PBA) offers polymer chemists something that proteins cannot: a small, inexpensive and thermally robust group that recognizes sugars and translates that recognition into a change in network charge and crosslink density. Hydrogels built around this group swell, contract or disassemble when the surrounding glucose concentration rises, and the process is reversible. Over roughly three decades the field has moved from proof-of-concept gels that only worked in alkaline buffer to materials that operate at pH 7.4 and 37 degrees C, and from bulk slabs to microgels, injectable networks, microneedle arrays, optical fibres and contact lenses. The present review collects that work. We start from the underlying chemistry, namely the trigonal-tetrahedral equilibrium of the boron centre, the way electron-withdrawing and ortho-aminomethyl substituents depress the pKa, and the selectivity problem created by fructose and other competing diols. Two synthetic routes are then compared: free-radical copolymerization of vinylic PBA monomers, and dynamic boronate-ester crosslinking of diol-rich polymers. Polysaccharide and protein backbones, which have dominated the last decade, are treated separately. Characterization is presented as a practical toolbox rather than a checklist, since FTIR, boron-11 NMR, alizarin red S displacement, electron microscopy, swelling kinetics, rheology and thermal analysis each answer a different question. The biological sections cover cytocompatibility, self-regulated insulin release in diabetic animals, glucose-responsive antioxidant and antibacterial dressings for diabetic wounds, sialic-acid-mediated tumour targeting, and continuous glucose monitoring. We close with the obstacles that still delay translation.
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