Convertible Hydrogel Injection Sequentially Regulates Diabetic Periodontitis.

Diabetes exacerbates periodontitis by overexpressing reactive oxygen species (ROS), which leads to periodontal bone resorption. Consequently, it is imperative to relieve inflammation and promote alveolar bone regeneration comprehensively for the development of diabetic periodontal treatment strategies. Furthermore, an orderly treatment to avoid interference between these two processes can achieve the optimal therapeutic effect. Thus, we constructed a sequential sustained release system based on the zeolitic imidazolate framework-8 (ZIF-8)-modified chitosan thermosensitive hydrogel (TOOTH) for diabetic periodontal therapy in this work. Chemically modified tetracycline-3 (CMT-3) and platelet-derived growth factor-BB (PDGF-BB) were loaded in the hydrogel and ZIF-8 for sequential release, respectively, with the aim of reducing inflammation and facilitating tissue regeneration. During the therapy, CMT-3 first escaped from the hydrogel due to degradation and diffusion for ROS elimination. Subsequently, ZIF-8 was dissociated under an acid microenvironment, and PDGF-BB was sustainably released to promote osteogenesis. The release intervals between CMT-3 and PDGF-BB could be regulated by the sizes of ZIF-8. The biocompatible TOOTH exhibited a favorable therapeutic effect for diabetic periodontitis in vitro and in vivo. The sequentially controlled release of CMT-3 and PDGF-BB facilitated by TOOTH holds promise for promoting periodontal tissue regeneration and offers potential for clinical translation.