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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.


Related in: MedlinePlus

Immunoassay: Quantification of secreted proteins. Secretion of (a) OPG, (b) VEGFA and (c) OC to cell culture medium from scaffolds with 10 nM and 10 µM SIM is shown in percentage of control, scaffolds without SIM, at 2, 8, 14 and 21 days. Values represent the mean ± SD. Statistical analysis: (a) p ≤ 0.05 versus alginate-coated scaffold without SIM.SIM: simvastatin; OPG: osteoprotegerin; OC: osteocalcin; VEGFA: vascular endothelial growth factor A; SD: standard deviation.
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fig6-2041731413515670: Immunoassay: Quantification of secreted proteins. Secretion of (a) OPG, (b) VEGFA and (c) OC to cell culture medium from scaffolds with 10 nM and 10 µM SIM is shown in percentage of control, scaffolds without SIM, at 2, 8, 14 and 21 days. Values represent the mean ± SD. Statistical analysis: (a) p ≤ 0.05 versus alginate-coated scaffold without SIM.SIM: simvastatin; OPG: osteoprotegerin; OC: osteocalcin; VEGFA: vascular endothelial growth factor A; SD: standard deviation.

Mentions: Culturing osteoblasts on SIM-containing scaffolds did not significantly change the ALP activity in the culture medium at any of the time points measured either for scaffolds with 10 nM or 10 µM SIM when compared to scaffolds without SIM (Figure 5(a)–(c)). No significant differences were seen in the OPG content of the culture medium at any of the time points either from scaffolds with 10 nM or 10 µM SIM when compared to scaffolds without SIM (Figure 6(a)). However, the content of VEGFA in the culture medium was significantly increased from osteoblasts cultured on scaffolds with both 10 nM and 10 µM SIM when compared to scaffolds without SIM at day 21 (p = 0.011, p = 0.014) (Figure 6(b)). The secretion of OC was significantly enhanced from osteoblasts on scaffolds with 10 µM SIM when compared to scaffolds without SIM (p = 0.048), whereas no significant difference was seen for osteoblasts cultured on scaffolds with 10 nM SIM compared to scaffolds without SIM after 21 days of culture (Figure 6(c)).


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)

Immunoassay: Quantification of secreted proteins. Secretion of (a) OPG, (b) VEGFA and (c) OC to cell culture medium from scaffolds with 10 nM and 10 µM SIM is shown in percentage of control, scaffolds without SIM, at 2, 8, 14 and 21 days. Values represent the mean ± SD. Statistical analysis: (a) p ≤ 0.05 versus alginate-coated scaffold without SIM.SIM: simvastatin; OPG: osteoprotegerin; OC: osteocalcin; VEGFA: vascular endothelial growth factor A; 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

fig6-2041731413515670: Immunoassay: Quantification of secreted proteins. Secretion of (a) OPG, (b) VEGFA and (c) OC to cell culture medium from scaffolds with 10 nM and 10 µM SIM is shown in percentage of control, scaffolds without SIM, at 2, 8, 14 and 21 days. Values represent the mean ± SD. Statistical analysis: (a) p ≤ 0.05 versus alginate-coated scaffold without SIM.SIM: simvastatin; OPG: osteoprotegerin; OC: osteocalcin; VEGFA: vascular endothelial growth factor A; SD: standard deviation.
Mentions: Culturing osteoblasts on SIM-containing scaffolds did not significantly change the ALP activity in the culture medium at any of the time points measured either for scaffolds with 10 nM or 10 µM SIM when compared to scaffolds without SIM (Figure 5(a)–(c)). No significant differences were seen in the OPG content of the culture medium at any of the time points either from scaffolds with 10 nM or 10 µM SIM when compared to scaffolds without SIM (Figure 6(a)). However, the content of VEGFA in the culture medium was significantly increased from osteoblasts cultured on scaffolds with both 10 nM and 10 µM SIM when compared to scaffolds without SIM at day 21 (p = 0.011, p = 0.014) (Figure 6(b)). The secretion of OC was significantly enhanced from osteoblasts on scaffolds with 10 µM SIM when compared to scaffolds without SIM (p = 0.048), whereas no significant difference was seen for osteoblasts cultured on scaffolds with 10 nM SIM compared to scaffolds without SIM after 21 days of culture (Figure 6(c)).

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.


Related in: MedlinePlus