Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis

Background: /Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesi...

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Main Authors: Xiao Liu, Naru Zhao, Haifeng Liang, Bizhi Tan, Fangli Huang, Hao Hu, Yan Chen, Gang Wang, Zemin Ling, Chun Liu, Yali Miao, Yingjun Wang, Xuenong Zou
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Journal of Orthopaedic Translation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214031X22001085
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author Xiao Liu
Naru Zhao
Haifeng Liang
Bizhi Tan
Fangli Huang
Hao Hu
Yan Chen
Gang Wang
Zemin Ling
Chun Liu
Yali Miao
Yingjun Wang
Xuenong Zou
author_facet Xiao Liu
Naru Zhao
Haifeng Liang
Bizhi Tan
Fangli Huang
Hao Hu
Yan Chen
Gang Wang
Zemin Ling
Chun Liu
Yali Miao
Yingjun Wang
Xuenong Zou
author_sort Xiao Liu
collection DOAJ
description Background: /Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesis and angiogenesis are coupled, a system of human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (hBMSCs) coculture is more biologically adapted to the microenvironment in vivo and can mediate osteogenesis and angiogenesis via paracrine signalling. Hence, in this study, a HUVECs/hBMSCs coculture system with appropriate cell and medium proportions was established. The substrate for the coculture system was a 3D-printed composite bioceramic scaffold (β-TCP/CaSiO3) based on a previous study. The aim of this study was to explore the potential of this system for bone tissue engineering. Methods: Bioactive ceramic scaffolds for tissue engineering were fabricated via a 3D Bioplotter™ system. The coculture system for in vitro and in vivo studies consisted of direct contact between HUVECs and hBMSCs cultured on the 3D-printed scaffolds. Results: The proportions of HUVECs/hBMSCs and medium components were determined by cell viability, and the coculture system showed negligible cytotoxicity. CD31 secreted by HUVECs formed strings, and cells tended to aggregate in island chain-like arrays. Real-time cell tracking showed that HUVECs were recruited by hBMSCs, and the integrin expression by HUVECs was upregulated. Ultimately, osteogenic and angiogenic marker gene expression and protein secretion were upregulated. Moreover, the obtained bone tissue engineering scaffolds could induce early osteogenic protein secretion and capillary tube formation in nude rats. Conclusion: These bone tissue engineering scaffolds without exogenous growth factors exhibited the ability to promote osteogenesis/angiogenesis. Translational potential of this article: The fabricated 3D-printed bioactive ceramic scaffolds could provide mechanical, biodegradable and bioadaptive support for personalized bone regeneration. In addition, the bone tissue engineering scaffolds exhibited the ability to promote osteogenesis/angiogenesis without the addition of exogenous growth factors, thus mitigating safety risks. Although application of the HUVECs/hBMSCs coculture system might be a time-consuming process, further development of cord blood storage could be beneficial for multicell coculture.
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spelling doaj.art-637f34500dbe4fda969381b482998b982023-01-05T06:24:09ZengElsevierJournal of Orthopaedic Translation2214-031X2022-11-0137152162Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesisXiao Liu0Naru Zhao1Haifeng Liang2Bizhi Tan3Fangli Huang4Hao Hu5Yan Chen6Gang Wang7Zemin Ling8Chun Liu9Yali Miao10Yingjun Wang11Xuenong Zou12Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaNational Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, China; School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, ChinaDepartment of Orthopedics, Zhujiang Hospital, Southern Medical University, No. 253 Industrial Avenue, Haizhu, Guangzhou, 510280, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Center for Translational Medicine, Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; Corresponding author. Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, China; School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Corresponding author. National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, China.Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Corresponding author.Background: /Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesis and angiogenesis are coupled, a system of human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (hBMSCs) coculture is more biologically adapted to the microenvironment in vivo and can mediate osteogenesis and angiogenesis via paracrine signalling. Hence, in this study, a HUVECs/hBMSCs coculture system with appropriate cell and medium proportions was established. The substrate for the coculture system was a 3D-printed composite bioceramic scaffold (β-TCP/CaSiO3) based on a previous study. The aim of this study was to explore the potential of this system for bone tissue engineering. Methods: Bioactive ceramic scaffolds for tissue engineering were fabricated via a 3D Bioplotter™ system. The coculture system for in vitro and in vivo studies consisted of direct contact between HUVECs and hBMSCs cultured on the 3D-printed scaffolds. Results: The proportions of HUVECs/hBMSCs and medium components were determined by cell viability, and the coculture system showed negligible cytotoxicity. CD31 secreted by HUVECs formed strings, and cells tended to aggregate in island chain-like arrays. Real-time cell tracking showed that HUVECs were recruited by hBMSCs, and the integrin expression by HUVECs was upregulated. Ultimately, osteogenic and angiogenic marker gene expression and protein secretion were upregulated. Moreover, the obtained bone tissue engineering scaffolds could induce early osteogenic protein secretion and capillary tube formation in nude rats. Conclusion: These bone tissue engineering scaffolds without exogenous growth factors exhibited the ability to promote osteogenesis/angiogenesis. Translational potential of this article: The fabricated 3D-printed bioactive ceramic scaffolds could provide mechanical, biodegradable and bioadaptive support for personalized bone regeneration. In addition, the bone tissue engineering scaffolds exhibited the ability to promote osteogenesis/angiogenesis without the addition of exogenous growth factors, thus mitigating safety risks. Although application of the HUVECs/hBMSCs coculture system might be a time-consuming process, further development of cord blood storage could be beneficial for multicell coculture.http://www.sciencedirect.com/science/article/pii/S2214031X22001085Bioactive ceramic scaffolds3D printingHUVECs/hBMSCs cocultureBone tissue engineering scaffoldsReal-time cell tracking
spellingShingle Xiao Liu
Naru Zhao
Haifeng Liang
Bizhi Tan
Fangli Huang
Hao Hu
Yan Chen
Gang Wang
Zemin Ling
Chun Liu
Yali Miao
Yingjun Wang
Xuenong Zou
Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
Journal of Orthopaedic Translation
Bioactive ceramic scaffolds
3D printing
HUVECs/hBMSCs coculture
Bone tissue engineering scaffolds
Real-time cell tracking
title Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
title_full Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
title_fullStr Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
title_full_unstemmed Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
title_short Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis
title_sort bone tissue engineering scaffolds with huvecs hbmscs cocultured on 3d printed composite bioactive ceramic scaffolds promoted osteogenesis angiogenesis
topic Bioactive ceramic scaffolds
3D printing
HUVECs/hBMSCs coculture
Bone tissue engineering scaffolds
Real-time cell tracking
url http://www.sciencedirect.com/science/article/pii/S2214031X22001085
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