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3D Printed Enzyme-Functionalized Scaffold Facilitates Diabetic Bone Regeneration
Authors:Chen Yang  Zhiwei Zheng  Muhammad Rizwan Younis  Chenle Dong  Yahong Chen  Shan Lei  Dong-Yang Zhang  Jiayingzi Wu  Xueqing Wu  Jing Lin  Xiansong Wang  Peng Huang
Affiliation:1. Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060 China;2. Department of Thoracic surgery, Shanghai Key Laboratory of Tissue Engineering, Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011 China;3. Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060 China

Department of Obstetrics and Gynecology, Shenzhen University General Hospital, Clinical Medical Academy, Shenzhen University, Shenzhen, 518060 China;4. Department of Obstetrics and Gynecology, Shenzhen University General Hospital, Clinical Medical Academy, Shenzhen University, Shenzhen, 518060 China

Abstract:Patients with diabetes mellitus (DM) suffer from a high risk of fractures and poor bone healing ability. Surprisingly, no effective therapy is available to treat diabetic bone defect in clinic. Here, a 3D printed enzyme-functionalized scaffold with multiple bioactivities including osteogenesis, angiogenesis, and anti-inflammation in diabetic conditions is proposed. The as-prepared multifunctional scaffold is constituted with alginate, glucose oxidase (GOx), and catalase-assisted biomineralized calcium phosphate nanosheets (CaP@CAT NSs). The GOx inside scaffolds can alleviate the hyperglycemia environment by catalyzing glucose and oxygen into gluconic acid and hydrogen peroxide (H2O2). Both the generated H2O2 as well as the overproduced H2O2 in DM can be scavenged by CaP@CAT NSs, while the initiated hypoxic microenvironment stimulates neovascularization. Moreover, the incorporation of CaP@CAT NSs not only enhance the mechanical property of the scaffolds, but also facilitate bone regeneration by the degraded Ca2+ and PO43? ions. The remarkable in vitro and in vivo outcomes demonstrate that enzymes functionalized scaffolds can be an effective strategy for enhancing bone tissue regeneration in diabetic conditions, underpinning the potential of multifunctional scaffolds for diabetic bone regeneration.
Keywords:3D printing  bone regeneration  catalase  diabetes  glucose oxidase
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