Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects

Bone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured...

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Main Authors: Tianlin Liu, Xin Zhang, Yuan Luo, Yuanliang Huang, Gang Wu
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1416047
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author Tianlin Liu
Xin Zhang
Yuan Luo
Yuanliang Huang
Gang Wu
author_facet Tianlin Liu
Xin Zhang
Yuan Luo
Yuanliang Huang
Gang Wu
author_sort Tianlin Liu
collection DOAJ
description Bone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured cellular foams-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SMC-PHBHHx) composite scaffold. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/allogeneic BMSCs for repairing critical-size bone defects in rats. In in vitro cellular experiments, icariin at optimal concentration (10−6 mol/L) could significantly upregulate the osteogenesis- and angiogenesis-related genes and proteins, such as Runx2, ALP, osteocalcin, vascular endothelial growth factors, and fibroblast growth factors, as well as the mineralization of BMSCs. Icariin that was adsorbed onto the SMC-PHBHHx scaffold showed a slow release profile within a 2-week monitoring span. Eight weeks after implantation in calvarial critical-size bone defects, the constructs with icariin were associated with significantly higher bone volume density, trabecular thickness, trabecular number, and significantly lower trabecular separation than the constructs without icariin. Histomorphometric analysis showed that icariin was also associated with a significantly higher density of newly formed blood vessels. These data suggested a promising application potential of the icariin/SMC-PHBHHx/allogeneic BMSCs constructs for repairing large-volume bone defects in clinic.
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spelling doaj-art-ff145b9b3bcb40b389e8d7fd3d617b2e2025-02-03T01:12:31ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/14160471416047Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone DefectsTianlin Liu0Xin Zhang1Yuan Luo2Yuanliang Huang3Gang Wu4Laboratory of Oral Biomedical Science and Translational Medicine, Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, ChinaStomatology Hospital Affiliated with Zhejiang University College of Medicine, Hangzhou, ChinaLaboratory of Oral Biomedical Science and Translational Medicine, Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, ChinaLaboratory of Oral Biomedical Science and Translational Medicine, Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, ChinaDepartment of Oral Implantology and Prosthetic Dentistry, Academic Center for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, NetherlandsBone tissue engineering technique is a promising strategy to repair large-volume bone defects. In this study, we developed a 3-dimensional construct by combining icariin (a small-molecule Chinese medicine), allogeneic bone marrow-derived mesenchymal stem cells (BMSCs), and a siliceous mesostructured cellular foams-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SMC-PHBHHx) composite scaffold. We hypothesized that the slowly released icariin could significantly promote the efficacy of SMC-PHBHHx/allogeneic BMSCs for repairing critical-size bone defects in rats. In in vitro cellular experiments, icariin at optimal concentration (10−6 mol/L) could significantly upregulate the osteogenesis- and angiogenesis-related genes and proteins, such as Runx2, ALP, osteocalcin, vascular endothelial growth factors, and fibroblast growth factors, as well as the mineralization of BMSCs. Icariin that was adsorbed onto the SMC-PHBHHx scaffold showed a slow release profile within a 2-week monitoring span. Eight weeks after implantation in calvarial critical-size bone defects, the constructs with icariin were associated with significantly higher bone volume density, trabecular thickness, trabecular number, and significantly lower trabecular separation than the constructs without icariin. Histomorphometric analysis showed that icariin was also associated with a significantly higher density of newly formed blood vessels. These data suggested a promising application potential of the icariin/SMC-PHBHHx/allogeneic BMSCs constructs for repairing large-volume bone defects in clinic.http://dx.doi.org/10.1155/2016/1416047
spellingShingle Tianlin Liu
Xin Zhang
Yuan Luo
Yuanliang Huang
Gang Wu
Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
Stem Cells International
title Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
title_full Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
title_fullStr Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
title_full_unstemmed Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
title_short Slowly Delivered Icariin/Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells to Promote the Healing of Calvarial Critical-Size Bone Defects
title_sort slowly delivered icariin allogeneic bone marrow derived mesenchymal stem cells to promote the healing of calvarial critical size bone defects
url http://dx.doi.org/10.1155/2016/1416047
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AT xinzhang slowlydeliveredicariinallogeneicbonemarrowderivedmesenchymalstemcellstopromotethehealingofcalvarialcriticalsizebonedefects
AT yuanluo slowlydeliveredicariinallogeneicbonemarrowderivedmesenchymalstemcellstopromotethehealingofcalvarialcriticalsizebonedefects
AT yuanlianghuang slowlydeliveredicariinallogeneicbonemarrowderivedmesenchymalstemcellstopromotethehealingofcalvarialcriticalsizebonedefects
AT gangwu slowlydeliveredicariinallogeneicbonemarrowderivedmesenchymalstemcellstopromotethehealingofcalvarialcriticalsizebonedefects