Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells

[Display omitted] There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their os...

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Veröffentlicht in:Acta biomaterialia 2019-04, Vol.89, p.359-371
Hauptverfasser: Heras, C., Sanchez-Salcedo, S., Lozano, D., Peña, J., Esbrit, P., Vallet-Regi, M., Salinas, A.J.
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container_issue
container_start_page 359
container_title Acta biomaterialia
container_volume 89
creator Heras, C.
Sanchez-Salcedo, S.
Lozano, D.
Peña, J.
Esbrit, P.
Vallet-Regi, M.
Salinas, A.J.
description [Display omitted] There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2–15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.
doi_str_mv 10.1016/j.actbio.2019.03.033
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In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2–15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. 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In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2–15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.</description><subject>Alkaline phosphatase</subject><subject>Angiogenesis</subject><subject>Bioceramics</subject><subject>Biocompatibility</subject><subject>Bioglass</subject><subject>Biological activity</subject><subject>Bone grafts</subject><subject>Bone growth</subject><subject>Bones</subject><subject>Cbfa-1 protein</subject><subject>Cell culture</subject><subject>Colonization</subject><subject>Differentiation (biology)</subject><subject>Fabrication</subject><subject>Grafts</subject><subject>Human mesenchymal cells</subject><subject>Ions</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchyme</subject><subject>Mesoporous bioactive glasses</subject><subject>Organic chemistry</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts</subject><subject>Osteostatin</subject><subject>Peptides</subject><subject>Phosphorus pentoxide</subject><subject>Porosity</subject><subject>Rapid prototyping</subject><subject>Regeneration</subject><subject>Regeneration (physiology)</subject><subject>Scaffolds</subject><subject>Silicon dioxide</subject><subject>Stem cells</subject><subject>Strategy</subject><subject>Structural hierarchy</subject><subject>Substitute bone</subject><subject>Synergistic effect</subject><subject>Tissue engineering</subject><subject>Zinc</subject><subject>Zinc oxide</subject><subject>ZnO</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kUuLVDEQhS-i4DjOP3ARcCPIbfO8STaCDM4DBmajm9mE3Dym09ybtKn0QPvrTdOuXAgFqcU5X1XlDMMHgjcEk-nLbmNdm1PZUEz0BrNe7NVwQZRUoxSTet17yeko8UTeDu8AdhgzRai6GH4_QgsFmm0po31pIbdkWwDUtgF1ZAenl9SOqES0Bij7UssB0PNiARA4G2NZPCBXcrMpp_yMnjL9jFLJgDpxe1htPhlDdtvjahfUx63IhWWB98ObaBcIV3_fy-Hnzfcf13fjw-Pt_fW3h9Exhds4zVYw5yWzM-FRO6-VEwJrj2dubcDeR62xxtH5mQvHhfB-mmwQEfuoVGCXw6czd1_Lr0OAZtYEpw1sDv0WQ4nmQkmuaZd-_Ee6K4ea-3aGUio5EZLIruJnlasFoIZo9jWtth4NweYUiNmZcyDmFIjBrBfrtq9nW-jHvqRQDbjU_yX4VINrxpf0f8AfwjSZSg</recordid><startdate>20190415</startdate><enddate>20190415</enddate><creator>Heras, C.</creator><creator>Sanchez-Salcedo, S.</creator><creator>Lozano, D.</creator><creator>Peña, J.</creator><creator>Esbrit, P.</creator><creator>Vallet-Regi, M.</creator><creator>Salinas, A.J.</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8408-3389</orcidid></search><sort><creationdate>20190415</creationdate><title>Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells</title><author>Heras, C. ; 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In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2–15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds with or without osteostatin were evaluated in hMCSs cultures. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications. Mesoporous bioactive glasses (MBGs) are bioceramics whose unique properties make them excellent materials for bone tissue engineering. Physico-chemical characterization of MBGs as scaffolds made by rapid prototyping, doped with zinc (potential osteogenic, angiogenic and bactericidal ion) and loaded with osteostatin (osteogenic peptide) are described. These Zn-MBGs scaffolds showed 3D hierarchical meso-macroporous structure that enables to host and release osteostatin. When decorated with human mesenchymal stem cells (hMSCs), MBGs scaffoldsenriched with both zinc and osteostatin exhibited a synergistic effect to enhance hMSCs growth, and also hMSCs osteogenic differentiationwithout addition of other osteoblastic differentiation factors to the culture medium. This novel strategy has a great potential for use in bone tissue engineering.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><doi>10.1016/j.actbio.2019.03.033</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8408-3389</orcidid><oa>free_for_read</oa></addata></record>
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subjects Alkaline phosphatase
Angiogenesis
Bioceramics
Biocompatibility
Bioglass
Biological activity
Bone grafts
Bone growth
Bones
Cbfa-1 protein
Cell culture
Colonization
Differentiation (biology)
Fabrication
Grafts
Human mesenchymal cells
Ions
Mesenchymal stem cells
Mesenchyme
Mesoporous bioactive glasses
Organic chemistry
Osteoblastogenesis
Osteoblasts
Osteostatin
Peptides
Phosphorus pentoxide
Porosity
Rapid prototyping
Regeneration
Regeneration (physiology)
Scaffolds
Silicon dioxide
Stem cells
Strategy
Structural hierarchy
Substitute bone
Synergistic effect
Tissue engineering
Zinc
Zinc oxide
ZnO
title Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells
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