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      Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine

      review-article
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      Frontiers in Bioengineering and Biotechnology
      Frontiers Media S.A.
      bone tissue engineering, biomaterials—cells, decellularizate ECM, polymer, stem cells—cartilage—bone marrow stem cells clinical application, mesenchymal stem cell

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          Abstract

          Bone is a dynamic organ with high regenerative potential and provides essential biological functions in the body, such as providing body mobility and protection of internal organs, regulating hematopoietic cell homeostasis, and serving as important mineral reservoir. Bone defects, which can be caused by trauma, cancer and bone disorders, pose formidable public health burdens. Even though autologous bone grafts, allografts, or xenografts have been used clinically, repairing large bone defects remains as a significant clinical challenge. Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of autografts and allografts. Ideal bone tissue engineering is to induce bone regeneration through the synergistic integration of biomaterial scaffolds, bone progenitor cells, and bone-forming factors. Successful stem cell-based BTE requires a combination of abundant mesenchymal progenitors with osteogenic potential, suitable biofactors to drive osteogenic differentiation, and cell-friendly scaffold biomaterials. Thus, the crux of BTE lies within the use of cell-friendly biomaterials as scaffolds to overcome extensive bone defects. In this review, we focus on the biocompatibility and cell-friendly features of commonly used scaffold materials, including inorganic compound-based ceramics, natural polymers, synthetic polymers, decellularized extracellular matrix, and in many cases, composite scaffolds using the above existing biomaterials. It is conceivable that combinations of bioactive materials, progenitor cells, growth factors, functionalization techniques, and biomimetic scaffold designs, along with 3D bioprinting technology, will unleash a new era of complex BTE scaffolds tailored to patient-specific applications.

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          Most cited references205

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          An overview of tissue and whole organ decellularization processes.

          Biologic scaffold materials composed of extracellular matrix (ECM) are typically derived by processes that involve decellularization of tissues or organs. Preservation of the complex composition and three-dimensional ultrastructure of the ECM is highly desirable but it is recognized that all methods of decellularization result in disruption of the architecture and potential loss of surface structure and composition. Physical methods and chemical and biologic agents are used in combination to lyse cells, followed by rinsing to remove cell remnants. Effective decellularization methodology is dictated by factors such as tissue density and organization, geometric and biologic properties desired for the end product, and the targeted clinical application. Tissue decellularization with preservation of ECM integrity and bioactivity can be optimized by making educated decisions regarding the agents and techniques utilized during processing. An overview of decellularization methods, their effect upon resulting ECM structure and composition, and recently described perfusion techniques for whole organ decellularization techniques are presented herein. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            The extracellular matrix at a glance.

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              Three-dimensional bioprinting of thick vascularized tissues.

              The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                14 December 2020
                2020
                : 8
                : 598607
                Affiliations
                [1] 1Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University , Qingdao, China
                [2] 2Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center , Chicago, IL, United States
                [3] 3Ministry of Education Key Laboratory of Diagnostic Medicine, The School of Laboratory Medicine and the Affiliated Hospitals, Chongqing Medical University , Chongqing, China
                [4] 4Department of Burn and Plastic Surgery, West China Hospital of Sichuan University , Chengdu, China
                [5] 5Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                [6] 6Departments of Orthopaedic Surgery and Neurosurgery, The Affiliated Zhongnan Hospital of Wuhan University , Wuhan, China
                [7] 7Department of Laboratory Diagnostic Medicine, The Affiliated Hospital of the University of Chinese Academy of Sciences, Chongqing General Hospital , Chongqing, China
                [8] 8Department of Orthopaedic Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [9] 9Department of Spine Surgery, Second Xiangya Hospital, Central South University , Changsha, China
                [10] 10Department of Surgery Section of Plastic and Reconstructive Surgery, The University of Chicago Medical Center , Chicago, IL, United States
                Author notes

                Edited by: Bin Li, Soochow University, China

                Reviewed by: Joaquim Miguel Oliveira, University of Minho, Portugal; Giovanni Vozzi, University of Pisa, Italy

                *Correspondence: Tong-Chuan He tche@ 123456uchicago.edu

                This article was submitted to Tissue Engineering and Regenerative Medicine, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2020.598607
                7767872
                33381499
                72bcc93b-ad53-46c4-9db6-292f6793896b
                Copyright © 2020 Zhang, Wu, Zhao, Pakvasa, Tucker, Luo, Qin, Hu, Wang, Li, Zhang, Mao, Sabharwal, He, Niu, Wang, Huang, Shi, Liu, Ni, Fu, Chen, Wagstaff, Reid, Athiviraham, Ho, Lee, Hynes, Strelzow, He and El Dafrawy.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 August 2020
                : 27 November 2020
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 205, Pages: 18, Words: 16282
                Categories
                Bioengineering and Biotechnology
                Review

                bone tissue engineering,biomaterials—cells,decellularizate ecm,polymer,stem cells—cartilage—bone marrow stem cells clinical application,mesenchymal stem cell

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