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Self-Mineralizing Dnazyme Hydrogel as a Multifaceted Bone Microenvironment Amendment for Promoting Osteogenesis in Osteoporosis
Authors:Haiping Wu  Shun Huang  Ying Zhu  Jia Li  Xiaoxiao Pang  Yongyao Tang  Siqiao Li  Ping Ji  Shijia Ding  Wei Cheng  Wenyang Li
Affiliation:1. The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 P.R. China

Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 P.R. China;2. Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Medical University, Chongqing, 401147 P.R. China;3. Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing Key Laboratory of Forensic Medicine, Chongqing Medical University, Chongqing, 400016 P.R. China;4. The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 P.R. China;5. Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 P.R. China

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.
Keywords:biomineralization  DNA hydrogels  microenvironment amendments  osteoporotic bone defects  zippered G4-hemin DNAzymes
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