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      Porous Silk Scaffolds for Delivery of Growth Factors and Stem Cells to Enhance Bone Regeneration

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          Abstract

          Stem cell-based tissue engineering shows promise for bone regeneration and requires artificial microenvironments to enhance the survival, proliferation and differentiation of the seeded cells. Silk fibroin, as a natural protein polymer, has unique properties for tissue regeneration. The present study aimed to evaluate the influence of porous silk scaffolds on rat bone marrow stem cells (BMSCs) by lenti-GFP tracking both in vitro and in vivo in cranial bone defects. The number of cells seeded within silk scaffolds in rat cranial bone defects increased from 2 days to 2 weeks after implantation, followed by a decrease at eight weeks. Importantly, the implanted cells survived for 8 weeks in vivo and some of the cells might differentiate into endothelial cells and osteoblasts induced by the presence of VEGF and BMP-2 in the scaffolds to promote angiogenesis and osteogenesis. The results demonstrate that porous silk scaffolds provide a suitable niche to maintain long survival and function of the implanted cells for bone regeneration.

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          Most cited references41

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          Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine.

          To date, 5 different human dental stem/progenitor cells have been isolated and characterized: dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), and dental follicle progenitor cells (DFPCs). These postnatal populations have mesenchymal-stem-cell-like (MSC) qualities, including the capacity for self-renewal and multilineage differentiation potential. MSCs derived from bone marrow (BMMSCs) are capable of giving rise to various lineages of cells, such as osteogenic, chondrogenic, adipogenic, myogenic, and neurogenic cells. The dental-tissue-derived stem cells are isolated from specialized tissue with potent capacities to differentiate into odontogenic cells. However, they also have the ability to give rise to other cell lineages similar to, but different in potency from, that of BMMSCs. This article will review the isolation and characterization of the properties of different dental MSC-like populations in comparison with those of other MSCs, such as BMMSCs. Important issues in stem cell biology, such as stem cell niche, homing, and immunoregulation, will also be discussed.
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            Tissue engineering.

            The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts to provide solutions to tissue creation and repair.
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              New opportunities for an ancient material.

              Spiders and silkworms generate silk protein fibers that embody strength and beauty. Orb webs are fascinating feats of bioengineering in nature, displaying magnificent architectures while providing essential survival utility for spiders. The unusual combination of high strength and extensibility is a characteristic unavailable to date in synthetic materials yet is attained in nature with a relatively simple protein processed from water. This biological template suggests new directions to emulate in the pursuit of new high-performance, multifunctional materials generated with a green chemistry and processing approach. These bio-inspired and high-technology materials can lead to multifunctional material platforms that integrate with living systems for medical materials and a host of other applications.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                22 July 2014
                : 9
                : 7
                : e102371
                Affiliations
                [1 ]Department of Prosthodontics, Ninth People's Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China
                [2 ]Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
                [3 ]Department of Oral and Stomatology, Linyi People's Hospital, Linyi, China
                [4 ]Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai, China
                [5 ]Department of Biomedical Engineering, School of Engineering, Tufts University, Medford, Massachusetts, United States of America
                National University of Ireland, Galway, Ireland
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: WZ DK XJ. Performed the experiments: WZ CZ DY LX Xiaochen Zhang QW. Analyzed the data: WZ CZ DY Xiaochen Zhang. Contributed reagents/materials/analysis tools: Xiuli Zhang DK XJ. Contributed to the writing of the manuscript: WZ CZ DK XJ.

                Article
                PONE-D-14-17646
                10.1371/journal.pone.0102371
                4106788
                25050556
                ed2faea2-a6a0-415e-a400-61c4890a8e29
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 April 2014
                : 17 June 2014
                Page count
                Pages: 9
                Funding
                This work was jointly supported by the National Basic Research Program of China (973 Program, 2012CB933604), Ph.D innovation fund from Shanghai Jiao Tong University School of Medicine (BXJ201331), the National Science Fund for Distinguished Young Scholars of China (No. 81225006), the National Natural Science Foundation of China (No. 81170939) and the National Institutes of Health (NIH P41 EB002520). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Engineering and Technology
                Bioengineering
                Biomedical Engineering
                Tissue Engineering
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. Data are available from the 'Shanghai Research Institute of Stomatology' Institutional Data Access/Ethics Committee for researchers who meet the criteria for access to confidential data. Data are from the 'Porous silk scaffolds for delivery of growth factors and stem cells to enhance bone regeneration' study whose authors may be contacted at xinquanj@ 123456aliyun.com .

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