Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair

Crosstalk between nerves and bone is essential for bone repair, for which Schwann cells (SCs) are crucial in the regulation of the microenvironment. Considering that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair, the aim of th...

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Main Authors: Tianchang Wang, Wentao Li, Yuxin Zhang, Xiang Xu, Lei Qiang, Weiqiang Miao, Xiaokun Yue, Xin Jiao, Xianhao Zhou, Zhenjiang Ma, Shuai Li, Muliang Ding, Junfeng Zhu, Chi Yang, Hui Wang, Tao Li, Xin Sun, Jinwu Wang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-09-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X23000518
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author Tianchang Wang
Wentao Li
Yuxin Zhang
Xiang Xu
Lei Qiang
Weiqiang Miao
Xiaokun Yue
Xin Jiao
Xianhao Zhou
Zhenjiang Ma
Shuai Li
Muliang Ding
Junfeng Zhu
Chi Yang
Hui Wang
Tao Li
Xin Sun
Jinwu Wang
author_facet Tianchang Wang
Wentao Li
Yuxin Zhang
Xiang Xu
Lei Qiang
Weiqiang Miao
Xiaokun Yue
Xin Jiao
Xianhao Zhou
Zhenjiang Ma
Shuai Li
Muliang Ding
Junfeng Zhu
Chi Yang
Hui Wang
Tao Li
Xin Sun
Jinwu Wang
author_sort Tianchang Wang
collection DOAJ
description Crosstalk between nerves and bone is essential for bone repair, for which Schwann cells (SCs) are crucial in the regulation of the microenvironment. Considering that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair, the aim of this study is to confirm the function and molecular mechanisms of Schwann cell-derived exosomes (SC-exos) on bone regeneration and to propose engineered constructs that simulate SC-mediated nerve–bone crosstalk. SCs promoted the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) through exosomes. Subsequent molecular mechanism studies demonstrated that SC-exos promoted BMSC osteogenesis by regulating the TGF-β signaling pathway via let-7c-5p. Interestingly, SC-exos promoted the migration and tube formation performance of endothelial progenitor cells. Furthermore, the SC-exos@G/S constructs were developed by bioprinting technology that simulated SC-mediated nerve–bone crosstalk and improved the bone regeneration microenvironment by releasing SC-exos, exerting the regulatory effect of SCs in the microenvironment to promote innervation, vascularization, and osteogenesis and thus effectively improving bone repair in a cranial defect model. This study demonstrates the important role and underlying mechanism of SCs in regulating bone regeneration through SC-exos and provides a new engineered strategy for bone repair.
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spelling doaj.art-1a3940e0fd8c4ada8301714ff62992312023-06-20T04:20:25ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-09-0127377393Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repairTianchang Wang0Wentao Li1Yuxin Zhang2Xiang Xu3Lei Qiang4Weiqiang Miao5Xiaokun Yue6Xin Jiao7Xianhao Zhou8Zhenjiang Ma9Shuai Li10Muliang Ding11Junfeng Zhu12Chi Yang13Hui Wang14Tao Li15Xin Sun16Jinwu Wang17Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaSports Medicine Department, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, No.49, North Garden Road, Haidian District, Beijing, 100191, China; Peking University Institute of Sports Medicine, No.49, North Garden Road, Haidian District, Beijing, 100191, ChinaDepartment of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaSchool of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaShanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou, 310003, ChinaDepartment of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, 410001, Hunan, ChinaDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, ChinaDepartment of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, ChinaInstitute of Rehabilitation Medicine, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201210, ChinaDepartment of Orthopedic Surgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China; Corresponding author.Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China; Corresponding author.Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China; Institute of Rehabilitation Medicine, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201210, China; Corresponding author. Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.Crosstalk between nerves and bone is essential for bone repair, for which Schwann cells (SCs) are crucial in the regulation of the microenvironment. Considering that exosomes are critical paracrine mediators for intercellular communication that exert important effects in tissue repair, the aim of this study is to confirm the function and molecular mechanisms of Schwann cell-derived exosomes (SC-exos) on bone regeneration and to propose engineered constructs that simulate SC-mediated nerve–bone crosstalk. SCs promoted the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) through exosomes. Subsequent molecular mechanism studies demonstrated that SC-exos promoted BMSC osteogenesis by regulating the TGF-β signaling pathway via let-7c-5p. Interestingly, SC-exos promoted the migration and tube formation performance of endothelial progenitor cells. Furthermore, the SC-exos@G/S constructs were developed by bioprinting technology that simulated SC-mediated nerve–bone crosstalk and improved the bone regeneration microenvironment by releasing SC-exos, exerting the regulatory effect of SCs in the microenvironment to promote innervation, vascularization, and osteogenesis and thus effectively improving bone repair in a cranial defect model. This study demonstrates the important role and underlying mechanism of SCs in regulating bone regeneration through SC-exos and provides a new engineered strategy for bone repair.http://www.sciencedirect.com/science/article/pii/S2452199X23000518Schwann cellsMicroenvironmentNerve–bone crosstalkExosomesBioprinting
spellingShingle Tianchang Wang
Wentao Li
Yuxin Zhang
Xiang Xu
Lei Qiang
Weiqiang Miao
Xiaokun Yue
Xin Jiao
Xianhao Zhou
Zhenjiang Ma
Shuai Li
Muliang Ding
Junfeng Zhu
Chi Yang
Hui Wang
Tao Li
Xin Sun
Jinwu Wang
Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
Bioactive Materials
Schwann cells
Microenvironment
Nerve–bone crosstalk
Exosomes
Bioprinting
title Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
title_full Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
title_fullStr Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
title_full_unstemmed Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
title_short Bioprinted constructs that simulate nerve–bone crosstalk to improve microenvironment for bone repair
title_sort bioprinted constructs that simulate nerve bone crosstalk to improve microenvironment for bone repair
topic Schwann cells
Microenvironment
Nerve–bone crosstalk
Exosomes
Bioprinting
url http://www.sciencedirect.com/science/article/pii/S2452199X23000518
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