Self‐Mineralizing Dnazyme Hydrogel as a Multifaceted Bone Microenvironment Amendment for Promoting Osteogenesis in Osteoporosis

Abstract The accumulation of reactive oxygen species (ROS) and minimal osteogenic raw material in the osteoporotic bone microenvironment greatly inhibits the activity of osteoblasts. Herein, it is originally proposed to construct a biomatrix multifaceted bone microenvironment amendment ‐Mineralized zippered G4‐Hemin DNAzyme hydrogel (MDH)‐to improve osteoporotic osteogenic capacity and promote high‐quality bone defect repair. The programmed design of the rolling circle amplified DNA hydrogel synthesis system allows the introduction of massive amounts of zippered G4‐Hemin DNAzyme in MDH. The zippered G4‐Hemin DNAzyme highly mimics the tight catalytic configuration of horseradish peroxidase and exerts excellent enzyme‐like activity with considerable ROS molecule scavenging ability. In addition, the DNA amplification by‐product pyrophosphate is ingeniously employed as a sufficient phosphorus source, thus constituting an autonomous mineralization system for waste reuse through the introduction of pyrophosphate hydrolase and calcium ions, which deposits in MDH as an osteogenic raw material and addresses the challenge of DNA hydrogel bio‐application stability. The remarkable in vitro and in vivo outcomes demonstrate that MDH can effectively improve the oxidative stress status of osteoblasts, restore the balance of mitochondrial membrane potential, and reduce apoptosis, ultimately demonstrating superior osteogenic capacity.