Abstract
Commonly used implants for therapeutic approaches of non-systemically impaired bone do not sufficiently support the healing process of osteoporotic bone. Since strontium (II) has been proven as an effective anti-osteoporotic drug new types of strontium enriched calcium phosphate bone cements were developed. As osteoporosis is characterized by an imbalance of osteoblast and osteoclast activity the influence of this newly generated strontium enriched biomaterials on the cellular behavior of osteoblast-like cells was investigated by time of flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS is used to analyze whether strontium is incorporated in the mineralized extracellular matrix (mECM) and whether there is strontium uptake by osteogenically differentiated human mesenchymal stem cells (hMSCs). Therefore hMSCs were cultured in osteogenic differentiation medium for 21 days on two different strontium enriched bone cements (S100 and A10) and for reference also on the pure calcium phosphate cement (CPC) and on a silicon wafer. The distribution of strontium in the osteoblast-like cells and within their mineralized extracellular matrix was analyzed. A higher intensity of the strontium signal could be detected in the region of the mECM, synthesized by cells cultivated on the Sr- substituted bone cement (S100) in comparison to the reference groups. The osteoblast-like cells used the released strontium from the biomaterial to synthesize their mECM. Apart from that a uniform strontium distribution was measured within all investigated cells. However, different amounts of strontium were found in cells cultured on different biomaterials and substrates. Compared to the negative controls the strontium content in the cells on the strontium enriched biomaterials was much higher. A higher concentration of strontium inside the cells means that more strontium can take part in signaling pathways. As strontium is known for its beneficial effects on osteoblasts by promoting osteoblastic cell replication and differentiation, and reducing apoptosis, the newly developed strontium enriched calcium phosphate cements are promising implant materials for osteoporotic bone.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-4106-8-17) contains supplementary material, which is available to authorized users.
Highlights
Osteoporosis is the most common type of systemic bone disease
We could demonstrate that the released strontium is incorporated into the mineralized extracellular matrix as well as enriched inside the osteogenically differentiated human mesenchymal stem cells (hMSCs)
In comparison to the control group we detected a definitely higher amount of strontium in the mineralized extracellular matrix (mECM) of the osteoblastlike cells cultured on the strontium substituted bone cement S100
Summary
Osteoporosis is the most common type of systemic bone disease. It is characterized by reduction of bone mineral density (BMD) and leads to an increased risk of fracture [1]. Adding an agent with anti-osteoporotic effects could improve the osseointegration of the implant which would cause a better fracture healing [7]. Clinical studies in postmenopausal osteoporotic patients showed a beneficial effect of orally administered strontium ranelate on fracture risk and micro architecture [14,15]. Li et al found an improvement of implant osseointegration in osteoporotic rats, which had an additional oral dispense of strontium ranelate [17]. In order to increase the local strontium dosage new types of strontium enriched calcium phosphate bone cements have recently been developed to achieve a local release of strontium ions into the bone defect [19]
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