Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic d...

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Main Authors: Shuaijie Li, Liyan Zhang, Chunyu Liu, Jua Kim, Kun Su, Tingli Chen, Limin Zhao, Xiaomei Lu, Hao Zhang, Yinglin Cui, Xu Cui, Feng Yuan, Haobo Pan
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-05-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X22004455
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author Shuaijie Li
Liyan Zhang
Chunyu Liu
Jua Kim
Kun Su
Tingli Chen
Limin Zhao
Xiaomei Lu
Hao Zhang
Yinglin Cui
Xu Cui
Feng Yuan
Haobo Pan
author_facet Shuaijie Li
Liyan Zhang
Chunyu Liu
Jua Kim
Kun Su
Tingli Chen
Limin Zhao
Xiaomei Lu
Hao Zhang
Yinglin Cui
Xu Cui
Feng Yuan
Haobo Pan
author_sort Shuaijie Li
collection DOAJ
description Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
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spelling doaj.art-5fa44c4cbe784a5b8ce87ab48180111d2024-04-16T17:25:32ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-05-0123101117Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defectsShuaijie Li0Liyan Zhang1Chunyu Liu2Jua Kim3Kun Su4Tingli Chen5Limin Zhao6Xiaomei Lu7Hao Zhang8Yinglin Cui9Xu Cui10Feng Yuan11Haobo Pan12Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China; Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaShenzhen Longhua District Central Hospital/the Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, 518110, ChinaDepartment of Orthopedics, Shanxi Bethune Hospital, Taiyuan, 030032, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, ChinaCenter for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China; Corresponding author.Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; Corresponding author.Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China; Shenzhen Key Laboratory of Marine Biomaterials, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China; Corresponding author. Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China.Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.http://www.sciencedirect.com/science/article/pii/S2452199X22004455Borosilicate glass bone cementImmunomodulationAngiogenesisOsteogenesis
spellingShingle Shuaijie Li
Liyan Zhang
Chunyu Liu
Jua Kim
Kun Su
Tingli Chen
Limin Zhao
Xiaomei Lu
Hao Zhang
Yinglin Cui
Xu Cui
Feng Yuan
Haobo Pan
Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
Bioactive Materials
Borosilicate glass bone cement
Immunomodulation
Angiogenesis
Osteogenesis
title Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
title_full Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
title_fullStr Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
title_full_unstemmed Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
title_short Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
title_sort spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by sr cu borosilicate glass bsg bone cement to repair critical bone defects
topic Borosilicate glass bone cement
Immunomodulation
Angiogenesis
Osteogenesis
url http://www.sciencedirect.com/science/article/pii/S2452199X22004455
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