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      Favorable osteogenic activity of iron doped in silicocarnotite bioceramic: In vitro and in vivo Studies

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          Abstract

          Background

          Calcium phosphate silicate (Ca 5(PO 4) 2SiO 4 or CPS) is a promising bioceramic for bone grafting. Iron (Fe) is a trace element in the human body that has been reported to enhance the mechanical strength of CPS ceramics. However, the exact biofunctions of Fe, combined with another human trace element, viz. silicon (Si), in CPS and the optimal dose for Fe addition must be further investigated.

          Methods

          In vitro: the morphology, structure and cell adhesion were observed by SEM; the ability to promote osteogenic differentiation and mineralization was explored by ALP and alizarin red staining; the expression of osteogenic-specific genes and proteins was detected by PCR, WB and immunofluorescence. In vivo: Further exploration of bone regeneration capacity by establishing a skull defect model.

          Results

          In vitro, we observed increased content of adhesion-related proteins and osteogenic-related genes expression of Fe-CPS compared with CPS, as demonstrated by immunofluorescence and polymerase chain reaction experiments, respectively. In vivo micro-computed tomography images, histomorphology, and undecalcified bone slicing also showed improved osteogenic ability of Fe-CPS bioceramics.

          Conclusion

          With the addition of Fe 2O 3, the new bone formation rate of the Fe-CPS scaffold after 12 weeks increased from 9.42% to 43.76%. Moreover, both in vitro and in vivo experimental outcomes indicated that Fe addition improved the CPS bioceramics in terms of their osteogenic ability by promoting the expression of osteogenic-related genes. Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability.

          The translational potential of this article

          This study suggests that Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability,which provides promising therapeutic implants and strategies for the treatment of large segmental bone defects.

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          Most cited references40

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          Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.

          Superparamagnetic iron oxide nanoparticles (SPION) with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, hyperthermia, drug delivery and in cell separation, etc. All these biomedical and bioengineering applications require that these nanoparticles have high magnetization values and size smaller than 100 nm with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. In addition, these applications need special surface coating of the magnetic particles, which has to be not only non-toxic and biocompatible but also allow a targetable delivery with particle localization in a specific area. To this end, most work in this field has been done in improving the biocompatibility of the materials, but only a few scientific investigations and developments have been carried out in improving the quality of magnetic particles, their size distribution, their shape and surface in addition to characterizing them to get a protocol for the quality control of these particles. Nature of surface coatings and their subsequent geometric arrangement on the nanoparticles determine not only the overall size of the colloid but also play a significant role in biokinetics and biodistribution of nanoparticles in the body. The types of specific coating, or derivatization, for these nanoparticles depend on the end application and should be chosen by keeping a particular application in mind, whether it be aimed at inflammation response or anti-cancer agents. Magnetic nanoparticles can bind to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumour using an external magnetic field or can be heated in alternating magnetic fields for use in hyperthermia. This review discusses the synthetic chemistry, fluid stabilization and surface modification of superparamagnetic iron oxide nanoparticles, as well as their use for above biomedical applications.
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            Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior.

            Calcium phosphate ceramics (CPCs) have been widely used as biomaterials for the regeneration of bone tissue because of their ability to induce osteoblastic differentiation in progenitor cells. Despite the progress made towards fabricating CPCs possessing a range of surface features and chemistries, the influence of material properties in orchestrating cellular events such as adhesion and differentiation is still poorly understood. Specifically, questions such as why certain CPCs may be more osteoinductive than others, and how material properties contribute to osteoinductivity/osteoconductivity remain unanswered. Therefore, this review article systematically discusses the effects of the physical (e.g. surface roughness) and chemical properties (e.g. solubility) of CPCs on protein adsorption, cell adhesion and osteoblastic differentiation in vitro. The review also provides a summary of possible signaling pathways involved in osteoblastic differentiation in the presence of CPCs. In summary, these insights on the contribution of material properties towards osteoinductivity and the role of signaling molecules involved in osteoblastic differentiation can potentially aid the design of CPC-based biomaterials that support bone regeneration without the need for additional biochemical supplements.
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              Bone regenerative medicine: classic options, novel strategies, and future directions

              This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future.
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                Author and article information

                Contributors
                Journal
                J Orthop Translat
                J Orthop Translat
                Journal of Orthopaedic Translation
                Chinese Speaking Orthopaedic Society
                2214-031X
                2214-0328
                15 February 2022
                January 2022
                15 February 2022
                : 32
                : 103-111
                Affiliations
                [a ]Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639# Zhizaoju Road, Shanghai, 200011, PR China
                [b ]The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, 100# Guilin Road, Shanghai, 200234, China
                [c ]State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Institute of Ceramics, Chinese Academy of Sciences, 1295# Dingxi Road, Shanghai, 200050, China
                [d ]Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600# Yishan Road, Shanghai, 200233, China
                Author notes
                []Corresponding author. huiwu1223@ 123456163.com
                [∗∗ ]Corresponding author. cqning@ 123456mail.sic.ac.cn
                [1]

                Both authors equally contributed to this work.

                Article
                S2214-031X(21)00105-4
                10.1016/j.jot.2021.12.002
                8856950
                35228992
                90f060ac-7e51-43ff-b5a5-80284b3075c3
                © 2021 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.

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

                History
                : 15 August 2021
                : 6 December 2021
                : 7 December 2021
                Categories
                Original Article

                bioceramic,bone formation,iron,osteogenic activity,silicocarnotite

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