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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Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2021-10-01
Series:Bioactive Materials
Subjects:
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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