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      The Bone Extracellular Matrix in Bone Formation and Regeneration

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          Abstract

          Bone regeneration repairs bone tissue lost due to trauma, fractures, and tumors, or absent due to congenital disorders. The extracellular matrix (ECM) is an intricate dynamic bio-environment with precisely regulated mechanical and biochemical properties. In bone, ECMs are involved in regulating cell adhesion, proliferation, and responses to growth factors, differentiation, and ultimately, the functional characteristics of the mature bone. Bone ECM can induce the production of new bone by osteoblast-lineage cells, such as MSCs, osteoblasts, and osteocytes and the absorption of bone by osteoclasts. With the rapid development of bone regenerative medicine, the osteoinductive, osteoconductive, and osteogenic potential of ECM-based scaffolds has attracted increasing attention. ECM-based scaffolds for bone tissue engineering can be divided into two types, that is, ECM-modified biomaterial scaffold and decellularized ECM scaffold. Tissue engineering strategies that utilize the functional ECM are superior at guiding the formation of specific tissues at the implantation site. In this review, we provide an overview of the function of various types of bone ECMs in bone tissue and their regulation roles in the behaviors of osteoblast-lineage cells and osteoclasts. We also summarize the application of bone ECM in bone repair and regeneration. A better understanding of the role of bone ECM in guiding cellular behavior and tissue function is essential for its future applications in bone repair and regenerative medicine.

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          Recent advances in bone tissue engineering scaffolds.

          Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, made of biodegradable materials that harbor different growth factors, drugs, genes, or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Scaffolds for Bone Tissue Engineering: State of the art and new perspectives.

            This review is intended to give a state of the art description of scaffold-based strategies utilized in Bone Tissue Engineering. Numerous scaffolds have been tested in the orthopedic field with the aim of improving cell viability, attachment, proliferation and homing, osteogenic differentiation, vascularization, host integration and load bearing. The main traits that characterize a scaffold suitable for bone regeneration concerning its biological requirements, structural features, composition, and types of fabrication are described in detail. Attention is then focused on conventional and Rapid Prototyping scaffold manufacturing techniques. Conventional manufacturing approaches are subtractive methods where parts of the material are removed from an initial block to achieve the desired shape. Rapid Prototyping techniques, introduced to overcome standard techniques limitations, are additive fabrication processes that manufacture the final three-dimensional object via deposition of overlying layers. An important improvement is the possibility to create custom-made products by means of computer assisted technologies, starting from patient's medical images. As a conclusion, it is highlighted that, despite its encouraging results, the clinical approach of Bone Tissue Engineering has not taken place on a large scale yet, due to the need of more in depth studies, its high manufacturing costs and the difficulty to obtain regulatory approval. PUBMED search terms utilized to write this review were: "Bone Tissue Engineering", "regenerative medicine", "bioactive scaffolds", "biomimetic scaffolds", "3D printing", "3D bioprinting", "vascularization" and "dentistry".
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              Proteoglycans: structures and interactions.

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                26 May 2020
                2020
                : 11
                : 757
                Affiliations
                [1] Laboratory for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Laboratory for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University , Xi'an, China
                Author notes

                Edited by: Zhong Zheng, University of California, Los Angeles, United States

                Reviewed by: Sing-Wai Wong, University of North Carolina at Chapel Hill, United States; Wenlu Jiang, University of California, Los Angeles, United States

                *Correspondence: Yong-Guang Gao, gaoyongguang@ 123456nwpu.edu.cn ; Airong Qian, qianair@ 123456nwpu.edu.cn

                †These authors have contributed equally to this work

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.00757
                7264100
                32528290
                9f4b296b-c070-4753-8824-c7dfa3f224e4
                Copyright © 2020 Lin, Patil, Gao and Qian

                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
                : 19 December 2019
                : 06 May 2020
                Page count
                Figures: 1, Tables: 5, Equations: 0, References: 119, Pages: 15, Words: 9007
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81700784, 81601913
                Funded by: Natural Science Foundation of Shaanxi Province 10.13039/501100007128
                Award ID: 2018JQ3049
                Funded by: Fundamental Research Funds for the Central Universities 10.13039/501100012226
                Award ID: 3102019ghxm012
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                ecm,bone formation,bone tissue engineering,bone repair,bone cells

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