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      Sustained release of naringin from silk-fibroin-nanohydroxyapatite scaffold for the enhancement of bone regeneration

      research-article
      a , a , , b , c , b , b
      Materials Today Bio
      Elsevier
      BTE, Bone tissue engineering, SF, silk fibroin, HAp, hydroxyapatite, PLGA, poly lactic-co-glycolic acid, BMSCs, Bone mesenchymal stem cells, HUVEC, human umbilical endothelial cells, PVA, Polyvinyl alcohol, SEM, scanning electron microscopy, CCK-8, Cell count kit-8, ALP, Alkaline phosphatase activity, RNA-Seq, RNA sequencing, GO, Gene ontology, BP, biological process, CC, cellular component, MF, molecular function, KEGG, Kyoto Encyclopedia of Genes and Genomes, DAVID, database for annotation, visualization, and integrated discovery, RT-PCR, real-time quantitative polymerase chain reaction, ANOVA, one-way analysis of variance, Naringin, Silk, Hydroxyapatite, Bone defect, PLGA, Microsphere

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          Abstract

          Bone defects are a common challenge in the clinical setting. Bone tissue engineering (BTE) is an effective treatment for the clinical problem of large bone defects. In this study, we fabricated silk fibroin (SF)/hydroxyapatite (HAp) scaffolds inlaid with naringin poly lactic-co-glycolic acid (PLGA) microspheres, investigating the feasibility of their application in BTE. Naringin PLGA microspheres were manufactured and adhered to the SF/HAp scaffold. Bone mesenchymal stem cells (BMSCs) were inoculated onto the SF/HAp scaffold containing naringin PLGA microsphere to examine the biocompatibility of the SF/HAp scaffolds. A rabbit femoral distal bone defect model was used to evaluate the in vivo function of the SF/HAp scaffolds containing naringin-loaded PLGA microspheres. The current study demonstrated that SF/HAp scaffolds containing naringin-loaded PLGA microspheres show promise as osteo-modulatory biomaterials for bone regeneration.

          Graphical abstract

          Overall schematic illustration of naringin microsphere silk fibroin/hydroxyapatite scaffold enhances BMSCs-based bone regeneration.

          Highlights

          • A novel porous composite scaffold was fabricated with naringin, SF and HAp.

          • MSN/SF/HAp scaffold shows promise as an osteo-modulatory biomaterial for bone regeneration.

          • MSN/SF/HAp scaffold exhibited osteogenic differentiation potential and is a promising candidate for tissue engineering.

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          Most cited references66

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            Endothelial Notch activity promotes angiogenesis and osteogenesis in bone.

            Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.
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              Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research.

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                Author and article information

                Contributors
                Journal
                Mater Today Bio
                Mater Today Bio
                Materials Today Bio
                Elsevier
                2590-0064
                23 January 2022
                January 2022
                23 January 2022
                : 13
                : 100206
                Affiliations
                [a ]Department of Orthopaedics, Tianjin Hospital, No. 406, Jiefangnan Road, Hexi District, Tianjin, 300000, China
                [b ]Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 122, Munan Road, Tianjin, 300050, China
                [c ]Department of Orthopedics, Jinhua Municipal Central Hospital, Jinhua, Zhejiang Province, China
                Author notes
                []Corresponding author. Department of Orthopaedics, Tianjin Hospital, No. 406, Jiefangnan Road, Hexi District, Tianjin, 300000, China. gukezzh@ 123456126.com
                Article
                S2590-0064(22)00004-7 100206
                10.1016/j.mtbio.2022.100206
                8808263
                35128373
                09df00d0-6b7c-414b-95c1-336b8a3d6371
                © 2022 The Authors

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

                History
                : 29 November 2021
                : 14 January 2022
                : 17 January 2022
                Categories
                Full Length Article

                bte, bone tissue engineering,sf, silk fibroin,hap, hydroxyapatite,plga, poly lactic-co-glycolic acid,bmscs, bone mesenchymal stem cells,huvec, human umbilical endothelial cells,pva, polyvinyl alcohol,sem, scanning electron microscopy,cck-8, cell count kit-8,alp, alkaline phosphatase activity,rna-seq, rna sequencing,go, gene ontology,bp, biological process,cc, cellular component,mf, molecular function,kegg, kyoto encyclopedia of genes and genomes,david, database for annotation, visualization, and integrated discovery,rt-pcr, real-time quantitative polymerase chain reaction,anova, one-way analysis of variance,naringin,silk,hydroxyapatite,bone defect,plga,microsphere

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