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      Bone tissue engineering via growth factor delivery: from scaffolds to complex matrices

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          Abstract

          In recent years, bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts. Bone tissue engineering provides a scaffold design that mimics the extracellular matrix, providing an architecture that guides the natural bone regeneration process. During this period, a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold, as well as osteogenic differentiation and angiogenesis, each of which is crucial to successful bone regeneration. Here, we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds. We also explore candidate materials used to fabricate these scaffolds. Different growth factors involved in the highly coordinated process of bone repair are discussed, and the key requirements of a growth factor delivery system are described. Finally, we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature. In particular, the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise, both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.

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          Most cited references78

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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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            Biomimetic porous scaffolds for bone tissue engineering

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              Bone tissue engineering: recent advances and challenges.

              The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field.
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                Author and article information

                Journal
                Regen Biomater
                Regen Biomater
                rb
                Regenerative Biomaterials
                Oxford University Press
                2056-3418
                2056-3426
                August 2018
                09 June 2018
                09 June 2018
                : 5
                : 4
                : 197-211
                Affiliations
                [1 ]Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA
                [2 ]Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Delft University of Technology (TU Delft), CD Delft, The Netherlands
                [3 ]McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA
                [4 ]Institute for Biomaterials, Drug Delivery and Regenerative Medicine, The University of Texas at Austin, Austin, TX, USA
                [5 ]Department of Pediatrics, and Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
                [6 ]Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
                Author notes
                Correspondence address. Department of Biomedical Engineering, The University of Texas at Austin, BME 3.503C, 107 W. Dean Keeton, BME Building, 1 University Station, C0800, Austin, TX 78712, USA. Tel: +1 512-471-6644; Fax: +1 512-471-8225; E-mail: peppas@ 123456che.utexas.edu
                Article
                rby013
                10.1093/rb/rby013
                6077800
                30094059
                2631cd5d-fe62-4c02-ab85-641213694b70
                © The Author(s) 2018. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 April 2018
                : 11 May 2018
                : 14 May 2018
                Page count
                Pages: 15
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01-EB022025
                Funded by: UT-Portugal Collaborative Research program
                Categories
                Reviews

                scaffolds,bone growth,tissue engineering,growth factor delivery

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