Osteoblastic differentiation of stem cells induced by graphene oxide-hydroxyapatite-alginate hydrogel composites and con

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TISSUE ENGINEERING CONSTRUCTS AND CELL SUBSTRATES Original Research

Osteoblastic differentiation of stem cells induced by graphene oxide-hydroxyapatite-alginate hydrogel composites and construction of tissue-engineered bone Xuanze Li1,2,3,4 Jiao Chen2,4 Zhe Xu1,4 Qiang Zou1,2,4 Long Yang1,2,4 Minxian Ma2,3,4 Liping Shu2,3,4 Zhixu He2 Chuan Ye 1,2,3,4,5 ●















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Received: 20 April 2020 / Accepted: 3 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract This study aimed to investigate the effect of graphene oxide (GO)-hydroxyapatite (HA)-sodium alginate (SA) composite application in the field of bone tissue engineering. Four scaffold groups were established (SA-HA, SA-HA-0.8%GO, SAHA-1.0%GO and SA-HA-1.2%GO) and mixed with bone marrow mesenchymal stem cells (BMSCs). Hydrogel viscosity was measured at room temperature, and after freeze-drying and Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) to detect substance crystallinity, the printability of each hydrogel type was measured with a printing grid. Scanning electron microscopy (SEM) was used to observe the internal microstructure of the scaffolds and to evaluate the growth and proliferation of cells on the scaffold. A hollow cylinder was printed to compare the forming effect of the hydrogel bioinks, and cell-hydrogel composites were implanted under the skin of nude mice to observe the effect of the hydrogels on osteogenesis in vivo. Increased GO concentrations led to reduced scaffold degradation rates, increased viscosity, increased printability, increased mechanical properties, increased scaffold porosity and increased cell proliferation rates. In vivo experiments showed that hematoxylin and eosin (HE) staining, Alizarin red staining, alkaline phosphatase staining and collagen type I immunohistochemical staining increased as the implantation time increased. These results demonstrate that GO composites have high printability as bioinks and can be used for bioprinting of bone by altering the ratio of the different components. Graphical Abstract

* Chuan Ye [email protected] 1

Department of Orthopaedics, The Affiliated Hospital of Guizhou Medical University, 550004 Guiyang, China

2

Key Laboratory of Adult Stem Cell Transformation Research, Chinese Academy of Medical Sciences, 550004 Guiyang, China

3

National-Local Joint Engineering Laboratory of Cell Engineering and Biomedicine, 550004 Guiyang, China

4

Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, 550004 Guiyang, China

5

China Orthopaedic Regenerative Medicine Group (CORMed), 310000 Hangzhou, China

125 Page 2 of 13

Journal of Materials Science: Materials in Medicine (2020)31:125

1 Introduction Tissue engineering is a rapidly developing field. Tissue regeneration requires degradable materials that meet biocompatibility requirements and scaffolds to support cell adhesion, differentiation, and growth [1, 2]. In bone tissue engineering, scaffolds are used