Injectable Adhesive Hydrogel through a Microcapsule Cross-Link for Periodontitis Treatment

In this work, chitosan (CS) decorated metronidazole (MTZ) microcapsules (CS@MTZ) were synthesized and used as a cross-linker for the preparation of a poly(vinyl alcohol) (PVA) injectable hydrogel by dynamic covalent bonding and ionic interaction through a 4-carboxyphenylboronic acid bridge. The use of MTZ microcapsules efficiently slowed down the release rate of the hydrophilic antibiotic from the hydrogel matrix. Besides, the hydrophobicity of the microcapsules endows the PVA@CS@MTZ hydrogel to be sticky to a substrate in wet conditions, under a suggested mechanism of evicting the water boundary layer on the substrate. The sustained release behavior endowed a prolonged bacteriostasis ability of the hydrogel formulation for up to 14 days in vitro, and the bioadhesive property as well as the injectability of the hydrogel benefited the topical delivery of MTZ in periodontal pockets and exhibited desirable antibacterial capacity in 1 week on the rat periodontitis model.