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      A standalone bioreactor system to deliver compressive load under perfusion flow to hBMSC-seeded 3D chitosan-graphene templates

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          Abstract

          The availability of engineered biological tissues holds great potential for both clinical applications and basic research in a life science laboratory. A prototype standalone perfusion/compression bioreactor system was proposed to address the osteogenic commitment of stem cells seeded onboard of 3D chitosan-graphene (CHT/G) templates. Testing involved the coordinated administration of a 1 mL/min medium flow rate together with dynamic compression (1% strain at 1 Hz; applied twice daily for 30 min) for one week. When compared to traditional static culture conditions, the application of perfusion and compression stimuli to human bone marrow stem cells using the 3D CHT/G template scaffold induced a sizable effect. After using the dynamic culture protocol, there was evidence of a larger number of viable cells within the inner core of the scaffold and of enhanced extracellular matrix mineralization. These observations show that our novel device would be suitable for addressing and investigating the osteogenic phenotype commitment of stem cells, for both potential clinical applications and basic research.

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          Most cited references36

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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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            Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

            The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
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              A decade of progress in tissue engineering.

              Tremendous progress has been achieved in the field of tissue engineering in the past decade. Several major challenges laid down 10 years ago, have been studied, including renewable cell sources, biomaterials with tunable properties, mitigation of host responses, and vascularization. Here we review advancements in these areas and envision directions of further development.
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                Author and article information

                Contributors
                joseph.lovecchio@unibo.it
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 November 2019
                14 November 2019
                2019
                : 9
                : 16854
                Affiliations
                [1 ]ISNI 0000 0004 0643 5232, GRID grid.9580.4, Institute of Biomedical and Neural Engineering, Reykjavík University, ; Menntavegur 1, 101 Reykiavík, Iceland
                [2 ]ISNI 0000 0004 1757 1758, GRID grid.6292.f, Laboratory of Cellular and Molecular Engineering “Silvio Cavalcanti” - Department of Electrical, Electronic and Information Engineering “Guglielmo Marconi” (DEI), University of Bologna, ; Via Cesare Pavese 50, 47522 Cesena, FC Italy
                [3 ]ISNI 0000 0004 1757 1758, GRID grid.6292.f, Advanced Research Center on Electronic Systems (ARCES), University of Bologna, ; Via Vincenzo Toffano 2/2, 40125 Bologna, Italy
                [4 ]ISNI 0000 0004 0643 5232, GRID grid.9580.4, Department of Science, , Reykjavík University, ; Menntavegur 1, 101 Reykiavík, Iceland
                [5 ]ISNI 0000 0004 1757 1758, GRID grid.6292.f, Health Sciences and Technologies - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, ; Via Tolara di Sopra 41/E, 40064 Ozzano dell’Emilia, BO Italy
                [6 ]ISNI 0000 0000 9894 0842, GRID grid.410540.4, The Blood Bank, The Landspitali University Hospital, ; Snorrabraut 60, 105 Reykjavík, Iceland
                [7 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Present Address: Center of Medical Physics and Biomedical Engineering, Medical University of Vienna, ; Waehringer Guertel 18-20/4L, 1090 Wien, Austria
                Author information
                http://orcid.org/0000-0002-4721-1388
                http://orcid.org/0000-0002-5049-4817
                Article
                53319
                10.1038/s41598-019-53319-7
                6856067
                31728040
                17becb0b-6de9-4ebb-8082-d29b06dfc06a
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 April 2019
                : 28 October 2019
                Categories
                Article
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                © The Author(s) 2019

                Uncategorized
                tissue engineering,biomedical engineering
                Uncategorized
                tissue engineering, biomedical engineering

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