ToF-SIMS analysis of osteoblast-like cells and their mineralized extracellular matrix on strontium enriched bone cements

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 material The online version of this article (doi:10.1186/1559-4106-8-17) contains supplementary material, which is available to authorized users.

In vivo and clinical application of strontium-enriched biomaterials for bone regeneration

“…51 Thormann et al 16 showed higher Sr concentrations in zones of increased bone formation, supporting this finding. More studies on the relationship between Sr concentrations and bone formation are needed to clarify this theory.…”

Histopathological evaluation of the effect of locally administered strontium on healing time in mandibular fractures: An experimental study

“…[23][24][25][26][27] Strontium that is incorporated into bone cements has been found to improve bone formation and reduce bone resorption in vivo. 28 Sabareeswaran et al investigated the bioactive fixation of strontium-containing glass ceramics and found out that it led to osseointegration during shortterm implementation. 29 Schumacher et al investigated the effect of strontium(II) released from calcium phosphate bone cement on primary human mesenchymal stem cells and reported that it could be useful for local therapy, particularly in osteoporotic bone.…”

Latest applications of 3D ToF-SIMS bio-imaging

“…A 2 keV oxygen etching beam was also used recently to perform 3D ToF-SIMS imaging to investigate the uptake of strontium from bone cements by osteoblast like cells. 36 In this study the oxygen beam was selected due to the increased ionization efficiency of the strontium ions despite the increased damage to molecular species compared with C 60 þ .…”