Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration.

ABSTRACT: Diabetes mellitus (DM) bone defects face impaired healing due to hyperglycemia, chronic inflammation, and dysregulated bone remodeling, yet existing therapies lack comprehensive strategies targeting these interconnected issues. Herein, a glucose/ROS-responsive multifunctional hydrogel (AAT-ZCG) is designed, integrating tannic acid (TA)-mediated dynamic borate ester bonds and a cascade nanozyme comprising cerium-zoledronic acid-glucose oxidase (ZCG). The hydrogel enables stimuli-responsive release of TA and ZCG within DM microenvironments, depleting glucose via glucose oxidase-mediated catalysis and mitigating inflammation through cerium-mediated ROS scavenging. Moreover, ZCG modulates macrophage polarization, stimulates angiogenesis and enhances osteogenesis. Acidic byproducts trigger ZCG

SUBMITTER: Fu X 

PROVIDER: S-EPMC12639025 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature