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Chitosan-miRNA Functionalized Microporous Titanium Oxide Surface via A Layer-by-layer Approach with a Sustained Release Profile for Enhanced Osteogenic Activity
Lingzhou Zhao
Fourth Military Medical University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Nanobiotechnology.
Background: Biofunctionalization of titanium implants for high osteogenic ability holds the hope for advanced implant of promoted osseointegration, especially in the compromised bone condition. In this study, using chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolyte, the polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach on the microarc oxidized (MAO) Ti surface via silane glutaraldehyde coupling.
Methods: Dynamic contact angle and scanning electron microscopy were firstly analyzed to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. In vitro transfection efficiency and cytotoxicity were investigated after mesenchymal stem cells (MSCs) being seeded on the CS-antimiR-138/HA PEM functionalized microporous Ti surface. The in vitro osteogenic differentiation of MSCs and in vivo osseointegration were also inspected.
Results: The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles distributed evenly along the MAO surface. The miRNA loading amount increased with the bilayer number increasing. More importantly, a sustained miRNA release of over approximately 2 week was obtained. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced osteogenic differentiation of MSCs on it in terms of enhanced alkaline phosphatase, collagen product and extracellular matrix mineralization. In the rat model, it led to dramatically enhanced in vivo osseointegration.
Conclusions: All these findings demonstrate that novel CS-antimiR-138/HA PEM functionalized microporous Ti implant exhibits sustained release of CS-antimiR-138, and obviously enhances the in vitro osteogenic differentiation of MSCs and dramatically enhanced in vivo osseointegration. This novel miRNA functionalized Ti implant may be used in clinic to allow more effective and robust osseointegration.
Keywords
microRNAs, sustained release, layer-by-layer, microarc oxidation, mesenchymal stem cells, titanium implants
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This preprint is under consideration at Journal of Nanobiotechnology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Chitosan-miRNA Functionalized Microporous Titanium Oxide Surface via A Layer-by-layer Approach with a Sustained Release Profile for Enhanced Osteogenic Activity
Lingzhou Zhao
Fourth Military Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 19 May, 2020
Published
On 09 Sep, 2020
No community comments so far
Editor assigned
On 16 May, 2020
Submission checks complete
On 15 May, 2020
Editor invited
On 15 May, 2020
First submitted
On 14 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nanoscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Nanobiotechnology.
Background: Biofunctionalization of titanium implants for high osteogenic ability holds the hope for advanced implant of promoted osseointegration, especially in the compromised bone condition. In this study, using chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolyte, the polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach on the microarc oxidized (MAO) Ti surface via silane glutaraldehyde coupling.
Methods: Dynamic contact angle and scanning electron microscopy were firstly analyzed to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. In vitro transfection efficiency and cytotoxicity were investigated after mesenchymal stem cells (MSCs) being seeded on the CS-antimiR-138/HA PEM functionalized microporous Ti surface. The in vitro osteogenic differentiation of MSCs and in vivo osseointegration were also inspected.
Results: The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles distributed evenly along the MAO surface. The miRNA loading amount increased with the bilayer number increasing. More importantly, a sustained miRNA release of over approximately 2 week was obtained. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced osteogenic differentiation of MSCs on it in terms of enhanced alkaline phosphatase, collagen product and extracellular matrix mineralization. In the rat model, it led to dramatically enhanced in vivo osseointegration.
Conclusions: All these findings demonstrate that novel CS-antimiR-138/HA PEM functionalized microporous Ti implant exhibits sustained release of CS-antimiR-138, and obviously enhances the in vitro osteogenic differentiation of MSCs and dramatically enhanced in vivo osseointegration. This novel miRNA functionalized Ti implant may be used in clinic to allow more effective and robust osseointegration.
Figure 1
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Figure 4
Figure 5
Figure 6
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Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13