282994 Synthesis and Characterization of Tri-Magnesium Phosphate (TMP) Novel Precursors to Biocompatible Bone Void Fillers

Monday, October 29, 2012: 10:54 AM
Cambria West (Westin )
Nicole Ostrowski, Abhijit Roy, Boeun Lee and Prashant Kumta, Bioengineering, University of Pittsburgh, Pittsburgh, PA

Synthesis and Characterization of Tri-Magnesium Phosphate (TMP) – Novel Precursors to Biocompatible Bone Void Fillers

Nicole J. Ostrowski- 1 (njo2@pitt.edu), Boeun Lee-1 (bol11@pitt.edu ), Abhijit Roy-1 (abr20@pitt.edu) , Prashant N. Kumta-1,2,3,4 (pkumta@pitt.edu)

1-Department of Bioengineering, University of Pittsburgh, Pittsburgh PA 15261, USA

2-Department of Chemical Engineering, University of Pittsburgh, Pittsburgh PA 15261, USA

3-Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh PA 15261, USA

4- Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh PA 15261, USA

            Bone substitutes are widely used in patients who require implantation to repair or remodel bone defects. These bone substitutes can range from synthetic materials such as metals, ceramics, synthetic polymers to natural polymeric materials including allografts and autografts. Calcium phosphate based synthetic grafts are an excellent choice of synthetic materials for bone replacement because these implants mimic the chemistry of the mineralized matrix of human bone and have shown excellent biocompatibility[1]. Synthetic calcium phosphate cements have been intensely studied due this chemical similarity and the injectability of many of the formulations, allowing for a reduction in the surgical site size and the filling of irregularly shaped voids. Currently, there are calcium phosphate based bone cements clinically available; however these products are less than ideal. Optimal bone cements would display high biocompatibility and osteoconductivity, strengths similar to human bone, resorption rates in line with rapid bone remodeling, and clinically relevant mixing and setting times and injectability[1]. Brushite-based calcium phosphate bone cements, although readily resorbable, tend to display compressive strengths lower than natural bone and extremely fast setting rates. Hydroxyapatite based calcium phosphate bone cements are capable of achieving higher strengths, but set very slowly and require years for resorption and remodeling[2,3]. Recently it has been proposed that magnesium phosphate cements may pose a more clinically favorable option to traditional calcium phosphate cements[4]. Preliminary studies have seen that magnesium phosphate based cements display higher strengths, better setting times and faster resorption rates than calcium phosphates while maintaining a high level of biocompatibility[4,5,6]. However, an in-depth study of magnesium phosphates and magnesium phosphate cements is currently limited. 

            This study explores the synthesis, material characteristics and inherent biocompatibility of trimagnesium phosphate (TMP), a critical reactant in magnesium phosphate bone void fillers.  Powdered magnesium phosphate was synthesized through a simple aqueous precipitation reaction and characterized for atomic content, crystallinity, degree of hydration and solubility. Materials analysis indicates consistent reproducible properties through multiple repetitions of synthesis, demonstrating a reliable method for synthesizing magnesium phosphate. Initial synthesis results in amorphous magnesium phosphate powder which crystallize upon heat treatment, yielding a single-phase magnesium phosphate Mg3(PO4)2.  As-synthesized amorphous magnesium phosphate demonstrates a Mg:P ratio of 1.5 with 30 wt% hydration. Solubility assessment performed on substrates of crystalline and amorphous TMP showed that crystalline TMP results in less release of magnesium ions than amorphous TMP over the span of several days. Biocompatibility of TMP was assessed through MTT cell activity assay and staining of live and dead cells.  Cytocompatibility testing shows the amorphous trimagnesium phosphate, to be non-toxic with osteoblast proliferation levels similar to calcium phosphate controls.  Subsequent experimentation will focus on the utilization of this amorphous magnesium phosphate for exploring cement reactions to create a commercially viable magnesium phosphate bone void filler.

References

[1] Low, K.L., Tan, S.H., Zein, S.H.S., Roether, J.A., Mourino, V., Boccaccini, A.R. Calcium phosphate-based composites as injectable bone substitute materials. J. Biomed. Materials Research B: Applied Biomaterials (2010); 98B(1): 273-286

[2] Vallet-Regi, M., Gonzalez-Calbet, J.M. Calcium phosphates as substitution of bone tissues. Prog Solid State Chem 2004; 32: 1-31

[3]Hofmann, M.P., Mohammed, A.R., Perrie, Y., Gbureck, U., Barralet, J.E. High-strength resorbable brushite bone cement with controlled drug-releasing capabilities. Acta Biomaterialia (2009); 5:43-49.

[4] Mestres, G., Ginebra, M.P. Novel magnesium phosphate cements with high early strength and antibacterial properties. Acta Biomaterialia (2011); 7: 1853-1861

[5] Yu, Y., Wan, J., Liu, C., Zhang, B., Chen, H., Buo, H., Zhong, G., Qu, W., Jiang, S., Huang, H. Evaluation of inherent toxicology and biocompatibility of magnesium phosphate bone cement. Colloids and Surfaces B: Biointerfaces 2010; 76: 496-504

[6]Driessens, F.C.M., Boltong, M.G., Zapatero, M.I., Verbeeck, R.M.H., Bonfield, W., Bermudez, O., Fernandez, E., Ginebra, M.P., Planell, J.A. In vivo behavior of three calcium phosphate cements and a magnesium phosphate cement. J. Mater Sci: Materials in Medicine (1995); 6:272-278.


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