Faculty Collaboration Database

In vitro osteogenesis by intracellular uptake of strontium containing bioactive glass nanoparticles. Acta Biomater 2018 Jan 15;66:67-80

Date

11/14/2017

Pubmed ID

29129790

DOI

10.1016/j.actbio.2017.11.008

Scopus ID

2-s2.0-85034031037 (requires institutional sign-in at Scopus site)   119 Citations

Abstract

UNLABELLED: Monodispersed strontium containing bioactive glass nanoparticles (Sr-BGNPs) with two compositions were synthesised, through a modified sol-gel Stöber process, wherein silica nanoparticles (SiO₂-NPs) were formed prior to incorporation of calcium and strontium, with diameters of 90 ± 10 nm. The osteogenic response of a murine preosteoblast cell line, MC3T3-E1, was investigated in vitro for a nanoparticle concentration of 250 µg/mL with compositions of 87 mol% SiO₂, 7 mol% CaO, 6 mol% SrO and 83 mol% SiO₂, 3 mol% CaO, 14 mol% SrO. Dissolution studies in minimum essential media (α-MEM) at pH 7.4 and artificial lysosomal fluid (ALF) at pH 4.5 showed that the particles dissolved and that Sr²⁺ ions were released from Sr-BGNPs in both environments. Both particle compositions and their ionic dissolution products enhanced the alkaline phosphatase (ALP) activity of the cells and calcium deposition. Immunohistochemistry (IHC) staining of Col1a1, osteocalcin (OSC) and osteopontin (OSP) showed that these proteins were expressed in the MC3T3-E1 cells following three weeks of culture. In the basal condition, the late osteogenic differentiation markers, OSC and OSP, were more overtly expressed by cells cultured with Sr-BGNPs with 14 mol% SrO and their ionic release products than in the control condition. Col1a1 expression was only slightly enhanced in the basal condition, but was enhanced further by the osteogenic supplements. These data demonstrate that Sr-BGNPs accelerate mineralisation without osteogenic supplements. Sr-BGNPs were internalised into MC3T3-E1 cells by endocytosis and stimulated osteogenic differentiation of the pre-osteoblast cell line. Sr-BGNPs are likely to be beneficial for bone regeneration and the observed osteogenic effects of these particles can be attributed to their ionic release products.

STATEMENT OF SIGNIFICANCE: We report, for the first time, that monodispersed bioactive glass nanoparticles (∼90 nm) are internalised into preosteoblast cells by endocytosis but by unspecific mechanisms. The bioactive nanoparticles and their dissolution products (without the particles present) stimulated the expression of osteogenic markers from preosteoblast cells without the addition of other osteogenic supplements. Incorporating Sr into the bioactive glass nanoparticle composition, in addition to Ca, increased the total cation content (and therefore dissolution rate) of the nanoparticles, even though nominal total cation addition was constant, without changing size or morphology. Increasing Sr content in the nanoparticles and in their dissolution products enhanced osteogenesis in vitro. The particles therefore have great potential as an injectable therapeutic for bone regeneration, particularly in patients with osteoporosis, for which Sr is known to be therapeutic agent.

Author List

Naruphontjirakul P, Porter AE, Jones JR

Author

Test W. User test user title in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Cell Death
Cell Differentiation
Cell Line
Ceramics
Dynamic Light Scattering
Endocytosis
Ions
Mice
Nanoparticles
Osteogenesis
Particle Size
Staining and Labeling
Static Electricity
Strontium
X-Ray Diffraction