Injectable strontium-modified calcium phosphate cement for the therapy of osteoporotic bone defectsWednesday (28.09.2016) 15:15 - 15:30 Part of:
Divalent strontium ions have gained considerable attention in osteoporosis therapy due to their dual mode of action on bone cells: they stimulate bone formation by osteoblasts and inhibit the osteoclastic bone resorption. Thus, Sr2+ could help to regulate the impaired balance of osteoblast and osteoclast activity characteristic for osteoporosis . The integration of Sr2+ into bone replacement materials ensures local delivery at the defect site and overcomes drawbacks of systemic administration. Recently, we have developed a strontium-containing calcium phosphate cement (SrCPC) that can easily be derived from a hydroxyapatite-forming cement by substitution of CaCO3 by SrCO3 in the precursor composition . The SrCPC has been shown to stimulate proliferation and osteogenic differentiation of human mesenchymal stromal cells (hMSC) in vitro and bone formation in critical size defects in ovariectomized rats [3,4].
However, this cement is based on a conventional powder/liquid approach which requires preparation of the cement paste immediately prior to surgical application. This bears the risk of low reproducibility and results in a narrow time window for processing. Therefore, the aim of the present work was to fabricate a ready-to-use paste by mixing the Sr2+-containing cement component with a water-immiscible carrier liquid mainly consisting of a biocompatible oil. This paste is stable over months; the setting reaction does not start before contact with aqueous solutions.
For material characterisation and in vitro experiments samples from a strontium-free reference paste (pCPC, InnoTERE) and the strontium-containing paste (pSrCPC) were prepared and set in water-saturated atmosphere to prevent early leaching of strontium ions. No significant differences in paste viscosity, setting behaviour and open porosity of the set cements were found between pCPC and pSrCPC. Mechanical characterisation revealed a slightly increased compressive strength for the strontium-modified cement after 3 days of setting; after 7 days pSrCPC reached 42 MPa compared to 36 MPa measured for pCPC. Cultivation of hMSC on the surface of pSrCPC resulted in higher cell numbers and increased alkaline phosphatase activity in comparison to pCPC. In conclusion, it could be demonstrated that the positive effect of strontium-modification on both mechanical and in vitro properties can be transferred from conventional powder/liquid-based cement to a new, ready-to-use injectable cement.
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This work was funded by the DFG as part of SFB Transregio 79 (subproject M2). The authors are grateful to InnoTERE GmbH (Radebeul) for the supply of material.