3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway

Wang，Lulu1; Shen，Mingkui1; Hou，Qiaodan1; Wu，Zimei1; Xu，Jing2; Wang，Lin1,2

2022-12-01

10.1016/j.ijbiomac.2022.09.236

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES   Impact Factor & Quartile

0141-8130

1879-0003

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.

3D printing Antioxidation Diabetic bone regeneration GelMA-g-GSH RNA sequencing analysis

SCI

English

First ; Corresponding

Basic and Applied Basic Research Foundation of Guangdong Province[2022A1515012373];National Natural Science Foundation of China[81972045];

Biochemistry & Molecular Biology ; Chemistry ; Polymer Science

Biochemistry & Molecular Biology ; Chemistry, Applied ; Polymer Science

WOS:000867226000002

ELSEVIER

BIOLOGY & BIOCHEMISTRY

2-s2.0-85139355609

Scopus

1.School of Medicine,Southern University of Science and Technology,Shenzhen,No. 1088 Xueyuan Avenue, Guangdong Province,518055,China
2.Southern University of Science and Technology Hospital,Shenzhen,6019 Liuxian Avenue,518055,China

Wang，Lulu,Shen，Mingkui,Hou，Qiaodan,et al. 3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2022,222:1175-1191.

Wang，Lulu,Shen，Mingkui,Hou，Qiaodan,Wu，Zimei,Xu，Jing,&Wang，Lin.(2022).3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,222,1175-1191.

Wang，Lulu,et al."3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 222(2022):1175-1191.