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      Bioinspired mineralized collagen scaffolds for bone tissue engineering

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          Abstract

          Successful regeneration of large segmental bone defects remains a major challenge in clinical orthopedics, thus it is of important significance to fabricate a suitable alternative material to stimulate bone regeneration. Due to their excellent biocompatibility, sufficient mechanical strength, and similar structure and composition of natural bone, the mineralized collagen scaffolds (MCSs) have been increasingly used as bone substitutes via tissue engineering approaches. Herein, we thoroughly summarize the state of the art of MCSs as tissue-engineered scaffolds for acceleration of bone repair, including their fabrication methods, critical factors for osteogenesis regulation, current opportunities and challenges in the future. First, the current fabrication methods for MCSs, mainly including direct mineral composite, in-situ mineralization and 3D printing techniques, have been proposed to improve their biomimetic physical structures in this review. Meanwhile, three aspects of physical (mechanics and morphology), biological (cells and growth factors) and chemical (composition and cross-linking) cues are described as the critical factors for regulating the osteogenic feature of MCSs. Finally, the opportunities and challenges associated with MCSs as bone tissue-engineered scaffolds are also discussed to point out the future directions for building the next generation of MCSs that should be endowed with satisfactorily mimetic structures and appropriately biological characters for bone regeneration.

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          Highlights

          • The recent progresses for building MCSs are recommended in detail.

          • Various regulation approaches are presented for enhancing the osteogenesis of MCSs.

          • The opportunities for MCSs as bone tissue-engineered scaffolds are discussed.

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          Most cited references210

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            3D bioprinting of tissues and organs.

            Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
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              Induced pluripotent stem cell lines derived from human somatic cells.

              Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.

                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                16 November 2020
                May 2021
                16 November 2020
                : 6
                : 5
                : 1491-1511
                Affiliations
                [a ]Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, PR China
                [b ]Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China
                [c ]Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100083, PR China
                [d ]Research Institute of Beihang University in Shenzhen, Shenzhen, 518057, PR China
                Author notes
                []Corresponding author. School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing, 100083, PR China. nxf@ 123456buaa.edu.cn
                [∗∗ ]Corresponding author. Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, No. 1068 Xueyuan Avenue, Nanshan District, Shenzhen, 518055, PR China. cs.ruan@ 123456siat.ac.cn
                Article
                S2452-199X(20)30293-0
                10.1016/j.bioactmat.2020.11.004
                7680706
                33294729
                4fcc0492-6347-414a-b99d-d566de7f4720
                © 2020 [The Author/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
                : 17 August 2020
                : 20 October 2020
                : 2 November 2020
                Categories
                Article

                collagen,mineralization,scaffold,bone repair,3d printing,biomechanics

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