Confocal microscope image of stem cells (nuclei are blue) containing therapeutic nanoparticles (green and inset) made of glass containing calcium and strontium ions. The nanoparticles and their dissolution ions send human bone marrow stem cells down an osteogenic route.Bone diseases like osteoporosis increase fracture risks, particularly amongst the elderly. In the USA alone, there are 1.5 million osteoporosis-related fractures a year and damage to hips or the spine can result in lifelong disability and high healthcare costs. Osteoporosis arises when the rates of bone resorption and formation are out of balance, leading to a reduction in overall bone mass. Treatments typically target bone resorption, using hormones (oestrogen) and bisphosphonates, which bind to bone mineral and inhibit resportion. Alternatively, bone-forming minerals like calcium and more recently strontium-containing drugs have been introduced.
Now researchers from the UK have combined the bone-growth promoting and bone-resportion inhibiting attributes of strontium (Sr) with bioglass, which is used for dental and orthopedic applications because of its bone cell stimulating properties. The team from Imperial College London and the University of Manchester observed that human-derived stem cells cultured with Sr-containing bioactive glass nanoparticles are stimulated to differentiate into osteogenic cells without the need for osteogenic supplements.
“Nanoparticles containing only silica and Sr provoked stem cells to become bone cells and to produce new bone matrix, which we confirmed by gene expression analysis, even without any other osteogenic supplements/growth factors added to the culture,” explains Julian R. Jones, who led the research. “When particles contain only silica and Ca, the stem cells did not differentiate.”
As well as the Sr-containing nanoparticles themselves, the researchers found that the resulting soup of ions created by dissolving the particles in media have the same effect on stem cells, provoking differentiation and bone formation. The results indicate, says Jones, that Sr ions play a crucial role in osteogenic differentiation of stem cells.
The 80-nm diameter Sr-containing bioglass nanoparticles are synthesized using an adapted sol-gel Stöber process in which a silica-based compound is reacted with water at controlled pH. Using microscopy and biological techniques, the team found that Sr-bioglass nanoparticles are taken into stem cells, where they end up localized within vesicles in the cytoplasm. The nanoparticles degrade in the acidic environment of the vesicles, releasing Sr and other ions.
“Bioactive glasses can be made quite cheaply and are stable,” points out Jones, “while nanoparticles could be injected or applied in a gel.”
The researchers think that such Sr-bioglass nanoparticles could form the basis of an injectable therapeutic treatment for bone diseases like osteoporosis, delivering a sustained dose of Sr ions to stimulate bone tissue regeneration.
“Nanoparticles could be used for hard to reach therapies and 3D printed scaffolds made of bioglass could be used to help the body repair bone defects,” says Jones. “Because the ions are found naturally in the body, this therapeutic approach could be safer than systemic drugs.”
Naruphontjirakul et al., Acta Biomaterialia (2019), https://doi.org/10.1016/j.actbio.2019.03.038