1. 3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway
- Author
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Lulu, Wang, Mingkui, Shen, Qiaodan, Hou, Zimei, Wu, Jing, Xu, and Lin, Wang
- Subjects
Bone Regeneration ,Tissue Scaffolds ,Tissue Engineering ,Hydrogels ,General Medicine ,Glutathione ,Biochemistry ,Diabetes Mellitus, Experimental ,Mice ,Phosphatidylinositol 3-Kinases ,Osteogenesis ,Structural Biology ,Printing, Three-Dimensional ,Animals ,Gelatin ,Methacrylates ,Reactive Oxygen Species ,Proto-Oncogene Proteins c-akt ,Molecular Biology ,Signal Transduction - Abstract
Diabetic individuals are frequently associated with increased fracture risk and poor bone healing capacity, and the treatment of diabetic bone defects remains a great challenge in orthopedics. In this study, an antioxidant hydrogel was developed using reduced glutathione grafted gelatine methacrylate (GelMA-g-GSH), followed by 3D printing to form a tissue engineering scaffold, which possessed appropriate mechanical property and good biocompatibility. In vitro studies displayed that benefitting from the sustained delivery of reduced glutathione, GelMA-g-GSH scaffold enabled to suppress the overproduction of reactive oxygen species (ROS) and reduce the oxidative stress of cells. Osteogenic experiments showed that GelMA-g-GSH scaffold exhibited excellent osteogenesis performance, with the elevated expression levels of osteogenesis-related genes and proteins. Further, RNA-sequencing revealed that activation of PI3K/Akt signaling pathway of MC3T3-E1 seeded on GelMA-g-GSH scaffold may be the underlying mechanism in promoting osteogenesis. In vivo, diabetic mice calvarial defects experiment demonstrated enhanced bone regeneration after the implantation of GelMA-g-GSH scaffold, as shown by micro-CT and histological analysis. In summary, 3D-printed GelMA-g-GSH scaffold can not only scavenge ROS, but also promote proliferation and differentiation of osteoblasts by activating PI3K/Akt signaling pathway, thereby accelerating bone repair under diabetes.
- Published
- 2022
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