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      Bioactive hydrogels for bone regeneration

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          Abstract

          Bone self-healing is limited and generally requires external intervention to augment bone repair and regeneration. While traditional methods for repairing bone defects such as autografts, allografts, and xenografts have been widely used, they all have corresponding disadvantages, thus limiting their clinical use. Despite the development of a variety of biomaterials, including metal implants, calcium phosphate cements (CPC), hydroxyapatite, etc., the desired therapeutic effect is not fully achieved. Currently, polymeric scaffolds, particularly hydrogels, are of interest and their unique configurations and tunable physicochemical properties have been extensively studied. This review will focus on the applications of various cutting-edge bioactive hydrogels systems in bone regeneration, as well as their advantages and limitations. We will examine the composition and defects of the bone, discuss the current biomaterials for bone regeneration, and classify recently developed polymeric materials for hydrogel synthesis. We will also elaborate on the properties of desirable hydrogels as well as the fabrication techniques and different delivery strategies. Finally, the existing challenges, considerations, and the future prospective of hydrogels in bone regeneration will be outlined.

          Graphical abstract

          Schematic illustration of hydrogel-assisted bone regeneration.

          Highlights

          • Microbeads have demonstrated great potential in encapsulating stem cells and drugs.

          • Nanogels delivered proteins to defects and effectively induced bone regeneration.

          • Hydrogel fibers have shown great promise in treating defects in load-bearing bones.

          • Stimuli-responsive hydrogel system is a novel technique in inducing bone formation.

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          Most cited references93

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          Classification, processing and application of hydrogels: A review.

          This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing. Super porous hydrogels (SPHs) and superabsorbent polymers (SAPs) represent an innovative category of recent generation highlighted as an ideal mould system for the study of solution-dependent phenomena. Hydrogels, also termed as smart and/or hungry networks, are currently subject of considerable scientific research due to their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields. Smart hydrogels display a significant physiochemical change in response to small changes in the surroundings. However, such changes are reversible; therefore, the hydrogels are capable of returning to its initial state after a reaction as soon as the trigger is removed.
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            Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover.

            Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.
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              Biomimetic porous scaffolds for bone tissue engineering

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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                26 May 2018
                December 2018
                26 May 2018
                : 3
                : 4
                : 401-417
                Affiliations
                [a ]Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P.R. China
                [b ]Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
                Author notes
                []Corresponding author. Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ07102, USA. xiaoyang.xu@ 123456njit.edu
                [∗∗ ]Corresponding author. Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P.R. China. xueqingzhang@ 123456sjtu.edu.cn
                [1]

                Xin Bai and Mingzhu Gao contributed equally to this work.

                Article
                S2452-199X(18)30026-4
                10.1016/j.bioactmat.2018.05.006
                6038268
                30003179
                234d8810-32e3-43be-a83e-165d43a2b4e0
                © 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 March 2018
                : 9 May 2018
                : 10 May 2018
                Categories
                Article

                bone regeneration,hydrogel,biomaterials,tissue engineering

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