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      Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds

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          Abstract

          Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.

          Graphical abstract

          Bone-tissue engineering has become a promising treatment strategy for large bone defects. This work first introduces the advanced knowledge of bone biology, including the physiological microenvironment and healing process. Based on this concept, it further details the current biomimetic and bioactive bone-tissue engineering scaffolds promoting the healing process. Finally, it provides the future perspective in this field.

          Highlights

          • Elaborate the advanced knowledge of bone physiological microenvironment and healing process.

          • Summary the biomolecules involved in the natural bone healing process which could be applied to BTE materials and scaffolds.

          • Detail the current biomimetic and bioinspired scaffolds based on the bone physiological microenvironment.

          • Review the delivery of bioactive factors based on the bone healing mechanism.

          • Discuss the current limitations that still need to be solved, and the feasible improvement and outlooks are proposed.

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          Most cited references347

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          Macrophage activation and polarization: nomenclature and experimental guidelines.

          Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Neutrophil recruitment and function in health and inflammation.

            Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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              Role of YAP/TAZ in mechanotransduction.

              Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                22 April 2021
                November 2021
                22 April 2021
                : 6
                : 11
                : 4110-4140
                Affiliations
                [a ]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China
                [b ]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610041, PR China
                Author notes
                []Corresponding author. zhzhao@ 123456scu.edu.cn
                [∗∗ ]Corresponding author. junliu@ 123456scu.edu.cn
                [∗∗∗ ]Corresponding author. yunbing.wang@ 123456scu.edu.cn
                [1]

                Equal contribution.

                Article
                S2452-199X(21)00154-7
                10.1016/j.bioactmat.2021.03.043
                8091181
                33997497
                a735ec76-8e34-4fb3-b267-f90e346587f0
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 24 February 2021
                : 19 March 2021
                : 28 March 2021
                Categories
                Article

                bone tissue engineering,scaffold,bone biology,cytokine,bone regeneration

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