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      Bioactive Factors-imprinted Scaffold Vehicles for Promoting Bone Healing: The Potential Strategies and the Confronted Challenges for Clinical Production

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          Abstract

          Wound repair of bone is a complicated multistep process orchestrated by inflammation, angiogenesis, callus formation, and bone remodeling. Many bioactive factors (BFs) including cytokine and growth factors (GFs) have previously been reported to be involved in regulating wound healing of bone and some exogenous BFs such as bone morphogenetic proteins (BMPs) were proven to be helpful for improving bone healing. In this regard, the BFs reported for boosting bone repair were initially categorized according to their regulatory mechanisms. Thereafter, the challenges including short half-life, poor stability, and rapid enzyme degradation and deactivation for these exogenous BFs in bone healing are carefully outlined in this review. For these issues, BFs-imprinted scaffold vehicles have recently been reported to promote the stability of BFs and enhance their half-life in vivo. This review is focused on the incorporation of BFs into the modulated biomaterials with various forms of bone tissue engineering applications: firstly, rigid bone graft substitutes (BGSs) were used to imprint BFs for large scale bone defect repair; secondly, the soft sponge-like scaffold carrying BFs is discussed as filling materials for the cavity of bone defects; thirdly, various injectable vehicles including hydrogel, nanoparticles, and microspheres for the delivery of BFs were also introduced for irregular bone fracture repair. Meanwhile, the challenges for BFs-imprinted scaffold vehicles are also analyzed in this review.

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          Most cited references 107

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          Hydrogels for tissue engineering.

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            Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery.

            In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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              Fracture healing under healthy and inflammatory conditions.

              Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation.
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                Author and article information

                Journal
                BIOI
                BIO Integration
                BIOI
                Compuscript (Ireland )
                2712-0082
                2712-0074
                01 June 2020
                15 June 2020
                : 1
                : 1
                : 37-54
                Affiliations
                1Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China
                2Department of Orthopaedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
                Author notes
                Correspondence to: Ying-Zheng Zhao, Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China. E-mail: pharmtds@ 123456163.com ; He-Lin Xu, Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China. E-mail: xhlpharm1214@ 123456126.com
                Article
                bioi20200010
                10.15212/bioi-2020-0010
                Copyright © 2020 Bio Integration

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See https://bio-integration.org/copyright-and-permissions/

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                Self URI (journal-page): https://bio-integration.org/
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