Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration
It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells (MSCs). However, the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear. This study aimed to investigate the effe...
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KeAi Communications Co., Ltd.
2021-10-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21000852 |
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author | Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J. Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu |
author_facet | Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J. Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu |
author_sort | Penghui Zhang |
collection | DOAJ |
description | It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells (MSCs). However, the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear. This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds. Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7, 14, or 21 days. At the predetermined time points, culture supernatant was collected for inflammatory mediator detection, and gene expression was analyzed by qRT-PCR. The results showed that the expression of inflammatory mediators (IL1B and IL8) was downregulated (p < 0.05) and the expression of ALP (p < 0.01) and COL1A1 (p < 0.05) was upregulated under mechanical loading. The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds (ECM-based scaffolds). Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization. The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers (Arginase 1 and Mrc1, p < 0.05) of macrophages in vitro and increased bone volume/total volume ratio in vivo. Overall, these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs. Besides, the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo. Mechanical loading may be a promising biofabrication strategy for bone biomaterials. |
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spelling | doaj.art-02f627dca76d4ff38372751f6cac7b4d2024-04-16T21:05:12ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-10-0161030973108Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regenerationPenghui Zhang0Xizhe Liu1Peng Guo2Xianlong Li3Zhongyuan He4Zhen Li5Martin J. Stoddart6Sibylle Grad7Wei Tian8Dafu Chen9Xuenong Zou10Zhiyu Zhou11Shaoyu Liu12Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaGuangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaInnovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaAO Research Institute Davos, Clavadelerstrasse 8, Davos, 7270, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, Davos, 7270, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, Davos, 7270, SwitzerlandLaboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, Beijing, 100035, ChinaLaboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, Beijing, 100035, China; Corresponding author.Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Corresponding author.Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Corresponding author. Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, China.Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute /Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, ChinaIt has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells (MSCs). However, the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear. This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds. Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7, 14, or 21 days. At the predetermined time points, culture supernatant was collected for inflammatory mediator detection, and gene expression was analyzed by qRT-PCR. The results showed that the expression of inflammatory mediators (IL1B and IL8) was downregulated (p < 0.05) and the expression of ALP (p < 0.01) and COL1A1 (p < 0.05) was upregulated under mechanical loading. The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds (ECM-based scaffolds). Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization. The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers (Arginase 1 and Mrc1, p < 0.05) of macrophages in vitro and increased bone volume/total volume ratio in vivo. Overall, these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs. Besides, the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo. Mechanical loading may be a promising biofabrication strategy for bone biomaterials.http://www.sciencedirect.com/science/article/pii/S2452199X21000852BioreactorBiofabricationInflammatory microenvironmentBone biomaterialsMacrophage polarization |
spellingShingle | Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J. Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration Bioactive Materials Bioreactor Biofabrication Inflammatory microenvironment Bone biomaterials Macrophage polarization |
title | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
title_full | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
title_fullStr | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
title_full_unstemmed | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
title_short | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
title_sort | effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration |
topic | Bioreactor Biofabrication Inflammatory microenvironment Bone biomaterials Macrophage polarization |
url | http://www.sciencedirect.com/science/article/pii/S2452199X21000852 |
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