Chitosan with phenolic hydroxyl groups (Chit-Ph) was synthesized by conjugating chitosan with 3-(p-hydroxyphenyl)propionic acid using aqueous-phase carbodiimide activation chemistry. By this conjugation, we could obtain chitosan derivatives soluble at neutral pH and gellable via a peroxidase-catalyzed reaction within seconds: The Chit-Ph with higher content of Ph groups showed higher solubility at neutral pH. The neutral Chit-Ph solutions gelated via an enzymatic reaction by consuming H₂O₂. The time necessary for gelation decreased with increasing content of Ph groups, temperature, peroxidase concentration, and decreasing H₂O₂ concentration. The content of Ph groups also influenced the mechanical property of the resultant gels. In addition, L929 cells, which were contacted to the enzymatically crosslinked Chit-Ph gels for 20 h, showed 96.5% viability, and were observed to grow next to the gels. These results demonstrate that Chit-Ph has the potency for use as injectable hydrogels in applications such as tissue engineering and drug delivery.

Glucose is a common component of body fluids. We describe a hydrogel wound dressing that can be obtained by pouring an aqueous solution of a polyvinyl alcohol derivative possessing phenolic hydroxyl moieties (PVA-Ph), containing glucose oxidase (GOx) and horseradish peroxidase (HRP), onto a wound. The in situ hydrogelation progresses through GOx-catalysed hydrogen peroxide (H₂O₂) generation from glucose in the wound exudate and HRP-catalysed cross-linking between phenolic hydroxyl moieties in PVA-Ph by consuming the H₂O₂. The potency as a wound dressing is demonstrated by experiments which reveal that the existence of the conditions inducing hydrogelation within 20 s at normal blood glucose concentration, the durability of the resultant hydrogels to compression and stretching, and the faster closure of full-thickness wounds created on rats treated with the in situ formed hydrogel than those treated by a commercially available hydrogel dressing.