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Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin.

Pullisaar H, Tiainen H, Landin MA, Lyngstadaas SP, Haugen HJ, Reseland JE, Ostrup E - J Tissue Eng (2013)

Bottom Line: No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin.The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days.In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway.

ABSTRACT
The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2) scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin) was quantified using real-time reverse transcriptase-polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex). The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 µM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.

No MeSH data available.


Simvastatin (SIM) release. Release profile of SIM from alginate-coated TiO2 scaffolds containing 2.4 mM and 0.6 mM SIM after 19-day incubation at 37°C. Bar graph shows the amount of SIM released after each time point. Line graph represents cumulative amount of SIM released up to 19 days. Values represent the mean ± SD.SD: standard deviation.
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fig3-2041731413515670: Simvastatin (SIM) release. Release profile of SIM from alginate-coated TiO2 scaffolds containing 2.4 mM and 0.6 mM SIM after 19-day incubation at 37°C. Bar graph shows the amount of SIM released after each time point. Line graph represents cumulative amount of SIM released up to 19 days. Values represent the mean ± SD.SD: standard deviation.

Mentions: The release of SIM was investigated for scaffolds with 2.4 mM and 0.6 mM SIM. A slow sustained release of SIM was detected for both concentrations. However, scaffolds with 2.4 mM SIM resulted, in a longer, 17-day release period compared to the 15-day release seen for scaffolds with 0.6 mM SIM (Figure 3). The cumulative release suggested that SIM remained entrapped in the alginate even after 19 days of incubation. Continued release could not be detected as the concentration after this point was below the detection limit.


Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin.

Pullisaar H, Tiainen H, Landin MA, Lyngstadaas SP, Haugen HJ, Reseland JE, Ostrup E - J Tissue Eng (2013)

Simvastatin (SIM) release. Release profile of SIM from alginate-coated TiO2 scaffolds containing 2.4 mM and 0.6 mM SIM after 19-day incubation at 37°C. Bar graph shows the amount of SIM released after each time point. Line graph represents cumulative amount of SIM released up to 19 days. Values represent the mean ± SD.SD: standard deviation.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC3927861&req=5

fig3-2041731413515670: Simvastatin (SIM) release. Release profile of SIM from alginate-coated TiO2 scaffolds containing 2.4 mM and 0.6 mM SIM after 19-day incubation at 37°C. Bar graph shows the amount of SIM released after each time point. Line graph represents cumulative amount of SIM released up to 19 days. Values represent the mean ± SD.SD: standard deviation.
Mentions: The release of SIM was investigated for scaffolds with 2.4 mM and 0.6 mM SIM. A slow sustained release of SIM was detected for both concentrations. However, scaffolds with 2.4 mM SIM resulted, in a longer, 17-day release period compared to the 15-day release seen for scaffolds with 0.6 mM SIM (Figure 3). The cumulative release suggested that SIM remained entrapped in the alginate even after 19 days of incubation. Continued release could not be detected as the concentration after this point was below the detection limit.

Bottom Line: No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin.The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days.In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway.

ABSTRACT
The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2) scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin) was quantified using real-time reverse transcriptase-polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex). The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 µM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.

No MeSH data available.