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Calcium-microRNA Complexes Functionalized Nanotubular Implant Surface for Highly Efficient Transfection and Enhanced Osteogenesis of Mesenchymal Stem Cells

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Calcium-microRNA Complexes Functionalized Nanotubular Implant Surface for Highly Efficient Transfection and Enhanced Osteogenesis of Mesenchymal Stem Cells. / Song, Wen; Yang, Chuanxu; Svend Le, Dang Quang; Zhang, Yumei; Kjems, Jørgen.

In: A C S Applied Materials and Interfaces, Vol. 10, No. 9, 07.03.2018, p. 7756-7764.

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@article{e9fed760f8324f11b50635fd0820c6d1,
title = "Calcium-microRNA Complexes Functionalized Nanotubular Implant Surface for Highly Efficient Transfection and Enhanced Osteogenesis of Mesenchymal Stem Cells",
abstract = "Controlling mesenchymal stem cells (MSCs) differentiation by RNA interference (RNAi) is a promising approach for next-generation regenerative medicine. However, efficient delivery of RNAi therapeutics is still a limiting factor. In this study, we have developed a simple, biocompatible and highly effective delivery method of small RNA therapeutics into hMSCs from an implant surface by calcium ions. First, we demonstrated that simple Ca/siGFP nanocomplexes were able to efficiently silence GFP in GFP-expressing hMSCs with adequate Ca2+ concentration (>5 mM). In addition, a single transfection could obtain a long-lasting silencing effect for more than two weeks. All three of the main endocytosis pathways (clathrin- and caveolin-mediated endocytosis and macropinocytosis) were involved in the internalization of the Ca/siRNA complexes by MSCs and macropinocytosis plays the most dominant role. Furthermore, the Ca/siRNA complexes could be efficiently loaded onto titanium implant surface when pre-treated with anodization to create a nanotubes (NTs) layer. Due to the hydrophilic property of the NTs surface, the Ca/siRNA was quickly loaded (less than 4 hours) with high efficiency (nearly 100{\%}) forming an even amorphous coating. Ca/siRNA coated NTs surface showed an initial burst release of 80{\%} of the siRNA complexes over 2 hours, which is adequate to achieve robust gene silencing of attached hMSCs. To demonstrate the therapeutic potential of our Ca/siRNA coating technology, Ca/antimiR-138 complexes were loaded on to NTs surface, which strongly enhanced osteogenic differentiation of hMSCs. In conclusion, our findings suggest that the Ca2+ is an effective and biocompatible carrier to deliver small RNA therapeutics into hMSCs, both in solution and from functionalized surfaces, which provide a novel approach to control the MSCs differentiation and tissue regeneration.",
keywords = "Journal Article",
author = "Wen Song and Chuanxu Yang and {Svend Le}, {Dang Quang} and Yumei Zhang and J{\o}rgen Kjems",
year = "2018",
month = "3",
day = "7",
doi = "10.1021/acsami.7b18289",
language = "English",
volume = "10",
pages = "7756--7764",
journal = "A C S Applied Materials and Interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",
number = "9",

}

RIS

TY - JOUR

T1 - Calcium-microRNA Complexes Functionalized Nanotubular Implant Surface for Highly Efficient Transfection and Enhanced Osteogenesis of Mesenchymal Stem Cells

AU - Song, Wen

AU - Yang, Chuanxu

AU - Svend Le, Dang Quang

AU - Zhang, Yumei

AU - Kjems, Jørgen

PY - 2018/3/7

Y1 - 2018/3/7

N2 - Controlling mesenchymal stem cells (MSCs) differentiation by RNA interference (RNAi) is a promising approach for next-generation regenerative medicine. However, efficient delivery of RNAi therapeutics is still a limiting factor. In this study, we have developed a simple, biocompatible and highly effective delivery method of small RNA therapeutics into hMSCs from an implant surface by calcium ions. First, we demonstrated that simple Ca/siGFP nanocomplexes were able to efficiently silence GFP in GFP-expressing hMSCs with adequate Ca2+ concentration (>5 mM). In addition, a single transfection could obtain a long-lasting silencing effect for more than two weeks. All three of the main endocytosis pathways (clathrin- and caveolin-mediated endocytosis and macropinocytosis) were involved in the internalization of the Ca/siRNA complexes by MSCs and macropinocytosis plays the most dominant role. Furthermore, the Ca/siRNA complexes could be efficiently loaded onto titanium implant surface when pre-treated with anodization to create a nanotubes (NTs) layer. Due to the hydrophilic property of the NTs surface, the Ca/siRNA was quickly loaded (less than 4 hours) with high efficiency (nearly 100%) forming an even amorphous coating. Ca/siRNA coated NTs surface showed an initial burst release of 80% of the siRNA complexes over 2 hours, which is adequate to achieve robust gene silencing of attached hMSCs. To demonstrate the therapeutic potential of our Ca/siRNA coating technology, Ca/antimiR-138 complexes were loaded on to NTs surface, which strongly enhanced osteogenic differentiation of hMSCs. In conclusion, our findings suggest that the Ca2+ is an effective and biocompatible carrier to deliver small RNA therapeutics into hMSCs, both in solution and from functionalized surfaces, which provide a novel approach to control the MSCs differentiation and tissue regeneration.

AB - Controlling mesenchymal stem cells (MSCs) differentiation by RNA interference (RNAi) is a promising approach for next-generation regenerative medicine. However, efficient delivery of RNAi therapeutics is still a limiting factor. In this study, we have developed a simple, biocompatible and highly effective delivery method of small RNA therapeutics into hMSCs from an implant surface by calcium ions. First, we demonstrated that simple Ca/siGFP nanocomplexes were able to efficiently silence GFP in GFP-expressing hMSCs with adequate Ca2+ concentration (>5 mM). In addition, a single transfection could obtain a long-lasting silencing effect for more than two weeks. All three of the main endocytosis pathways (clathrin- and caveolin-mediated endocytosis and macropinocytosis) were involved in the internalization of the Ca/siRNA complexes by MSCs and macropinocytosis plays the most dominant role. Furthermore, the Ca/siRNA complexes could be efficiently loaded onto titanium implant surface when pre-treated with anodization to create a nanotubes (NTs) layer. Due to the hydrophilic property of the NTs surface, the Ca/siRNA was quickly loaded (less than 4 hours) with high efficiency (nearly 100%) forming an even amorphous coating. Ca/siRNA coated NTs surface showed an initial burst release of 80% of the siRNA complexes over 2 hours, which is adequate to achieve robust gene silencing of attached hMSCs. To demonstrate the therapeutic potential of our Ca/siRNA coating technology, Ca/antimiR-138 complexes were loaded on to NTs surface, which strongly enhanced osteogenic differentiation of hMSCs. In conclusion, our findings suggest that the Ca2+ is an effective and biocompatible carrier to deliver small RNA therapeutics into hMSCs, both in solution and from functionalized surfaces, which provide a novel approach to control the MSCs differentiation and tissue regeneration.

KW - Journal Article

U2 - 10.1021/acsami.7b18289

DO - 10.1021/acsami.7b18289

M3 - Journal article

VL - 10

SP - 7756

EP - 7764

JO - A C S Applied Materials and Interfaces

JF - A C S Applied Materials and Interfaces

SN - 1944-8244

IS - 9

ER -