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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      3D Printing of Micro- and Nanoscale Bone Substitutes: A Review on Technical and Translational Perspectives

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          Abstract

          Recent developments in three-dimensional (3D) printing technology offer immense potential in fabricating scaffolds and implants for various biomedical applications, especially for bone repair and regeneration. As the availability of autologous bone sources and commercial products is limited and surgical methods do not help in complete regeneration, it is necessary to develop alternative approaches for repairing large segmental bone defects. The 3D printing technology can effectively integrate different types of living cells within a 3D construct made up of conventional micro- or nanoscale biomaterials to create an artificial bone graft capable of regenerating the damaged tissues. This article reviews the developments and applications of 3D printing in bone tissue engineering and highlights the numerous conventional biomaterials and nanomaterials that have been used in the production of 3D-printed scaffolds. A comprehensive overview of the 3D printing methods such as stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and ink-jet 3D printing, and their technical and clinical applications in bone repair and regeneration has been provided. The review is expected to be useful for readers to gain an insight into the state-of-the-art of 3D printing of bone substitutes and their translational perspectives.

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          Most cited references266

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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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            Porosity of 3D biomaterial scaffolds and osteogenesis.

            Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be approximately 100 microm due to cell size, migration requirements and transport. However, pore sizes >300 microm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vascularization, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
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              3D printing of polymer matrix composites: A review and prospective

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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                ijn
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                24 June 2021
                2021
                : 16
                : 4289-4319
                Affiliations
                [1 ]School of Basic Medicine, Chengdu University , Chengdu, 610106, People’s Republic of China
                [2 ]Biomaterials and Organ Engineering Group, Centre for Biomaterials, Cellular, and Molecular Theranostics, School of Bio Sciences and Technology, Vellore Institute of Technology , Vellore, Tamil Nadu, 632014, India
                [3 ]Department of Radiological Sciences, University of California Los Angeles , Los Angeles, CA, 90095, USA
                [4 ]Department of Chemical Engineering, University of Massachusetts Lowell , Lowell, MA, 01854, USA
                Author notes
                Correspondence: Lijia Cheng School of Basic Medicine, Chengdu University , Chengdu, 610106, People’s Republic of China Email chenglijia@cdu.edu.cn
                Murugan Ramalingam Biomaterials & Organ Engineering Group, Centre for Biomaterials, Cellular, and Molecular Theranostics, Vellore Institute of Technology , Vellore, Tamil Nadu, 632014, IndiaTel +91-416-220-2736Fax +91-416-2243092 Email rmurug2000@gmail.com
                Author information
                http://orcid.org/0000-0002-4412-6807
                http://orcid.org/0000-0003-4649-5371
                http://orcid.org/0000-0002-4189-8086
                Article
                311001
                10.2147/IJN.S311001
                8239380
                34211272
                2d6542a2-a8d5-418a-a981-eb5be47e73f5
                © 2021 Cheng et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 16 March 2021
                : 17 May 2021
                Page count
                Figures: 11, Tables: 1, References: 267, Pages: 31
                Categories
                Review

                Molecular medicine
                3d printing,artificial bone,bone tissue engineering,biomaterials,nanomaterials
                Molecular medicine
                3d printing, artificial bone, bone tissue engineering, biomaterials, nanomaterials

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