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      3D printing of Haversian bone–mimicking scaffolds for multicellular delivery in bone regeneration

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          Abstract

          Tissue engineering scaffolds are supposed to mimick the native tissue to achieve the functionalized tissue regeneration.

          Abstract

          The integration of structure and function for tissue engineering scaffolds is of great importance in mimicking native bone tissue. However, the complexity of hierarchical structures, the requirement for mechanical properties, and the diversity of bone resident cells are the major challenges in constructing biomimetic bone tissue engineering scaffolds. Herein, a Haversian bone–mimicking scaffold with integrated hierarchical Haversian bone structure was successfully prepared via digital laser processing (DLP)–based 3D printing. The compressive strength and porosity of scaffolds could be well controlled by altering the parameters of the Haversian bone–mimicking structure. The Haversian bone–mimicking scaffolds showed great potential for multicellular delivery by inducing osteogenic, angiogenic, and neurogenic differentiation in vitro and accelerated the ingrowth of blood vessels and new bone formation in vivo. The work offers a new strategy for designing structured and functionalized biomaterials through mimicking native complex bone tissue for tissue regeneration.

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          Most cited references32

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          Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing

          Although three-dimensional (3D) bioprinting technology has gained much attention in the field of tissue engineering, there are still several significant engineering challenges to overcome, including lack of bioink with biocompatibility and printability. Here, we show a bioink created from silk fibroin (SF) for digital light processing (DLP) 3D bioprinting in tissue engineering applications. The SF-based bioink (Sil-MA) was produced by a methacrylation process using glycidyl methacrylate (GMA) during the fabrication of SF solution. The mechanical and rheological properties of Sil-MA hydrogel proved to be outstanding in experimental testing and can be modulated by varying the Sil-MA contents. This Sil-MA bioink allowed us to build highly complex organ structures, including the heart, vessel, brain, trachea and ear with excellent structural stability and reliable biocompatibility. Sil-MA bioink is well-suited for use in DLP printing process and could be applied to tissue and organ engineering depending on the specific biological requirements.
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            Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies.

            The development of responsive biomaterials capable of demonstrating modulated function in response to dynamic physiological and mechanical changes in vivo remains an important challenge in bone tissue engineering. To achieve long-term repair and good clinical outcomes, biologically responsive approaches that focus on repair and reconstitution of tissue structure and function through drug release, receptor recognition, environmental responsiveness and tuned biodegradability are required. Traditional orthopedic materials lack biomimicry, and mismatches in tissue morphology, or chemical and mechanical properties ultimately accelerate device failure. Multiple stimuli have been proposed as principal contributors or mediators of cell activity and bone tissue formation, including physical (substrate topography, stiffness, shear stress and electrical forces) and biochemical factors (growth factors, genes or proteins). However, optimal solutions to bone regeneration remain elusive. This review will focus on biological and physicomechanical considerations currently being explored in bone tissue engineering.
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              Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis

              Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                March 2020
                20 March 2020
                : 6
                : 12
                : eaaz6725
                Affiliations
                [1 ]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China.
                [2 ]Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
                [3 ]Beijing Ten Dimensions Technology Co., Ltd., Beijing 100084, P. R. China.
                Author notes
                [* ]Corresponding author. Email: chengtiewu@ 123456mail.sic.ac.cn
                Author information
                http://orcid.org/0000-0002-4733-3238
                http://orcid.org/0000-0003-1462-6541
                http://orcid.org/0000-0002-5986-591X
                Article
                aaz6725
                10.1126/sciadv.aaz6725
                7083611
                32219170
                ad332034-4a1b-43e6-beda-00f8bcc192cb
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 29 September 2019
                : 23 December 2019
                Funding
                Funded by: doi http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81771989
                Funded by: doi http://dx.doi.org/10.13039/501100003399, Science and Technology Commission of Shanghai Municipality;
                Award ID: 17540712300
                Funded by: doi http://dx.doi.org/10.13039/501100003399, Science and Technology Commission of Shanghai Municipality;
                Award ID: 17540712300
                Funded by: doi http://dx.doi.org/10.13039/501100013290, National Key Research and Development Program of China Stem Cell and Translational Research;
                Award ID: 2018YFC1105201
                Funded by: Innovation Cross Team of Chinese Academy of Sciences;
                Award ID: JCTD-2018-13
                Funded by: STS Program of Chinese Academy of Sciences;
                Award ID: KFJ-STS-QYZD-092
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Materials Science
                Applied Sciences and Engineering
                Applied Sciences and Engineering
                Custom metadata
                Sef Rio

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