Unravelling the Effect of Citrate on the Features and Biocompatibility of Magnesium Phosphate-Based Bone Cements

In the framework of new materials for orthopedic applications, Magnesium Phosphate-based Cements (MPCs) are currently the focus of active research in biomedicine, given their promising features; in this field, the loading of MPCs with active molecules to be released in the proximity of newly forming bone could represent an innovative approach to enhance the in vivo performances of the biomaterial. In this work, we describe the preparation and characterization of MPCs containing citrate, an ion naturally present in bone which presents beneficial effects when released in the proximity of newly forming bone tissue. The cements were characterized in terms of handling properties, setting time, mechanical properties, crystallinity, and microstructure, so as to unravel the effect of citrate concentration on the features of the material. Upon incubation in aqueous media, we demonstrated that citrate could be successfully released from the cements, while contributing to the alkalinization of the surroundings. The cytotoxicity of the materials toward human fibroblasts was also tested, revealing the importance of a fine modulation of released citrate to guarantee the biocompatibility of the material.

[1]  N. Baldini,et al.  Role of Citrate in Pathophysiology and Medical Management of Bone Diseases , 2019, Nutrients.

[2]  P. Baglioni,et al.  Formation and properties of amorphous magnesium-calcium phosphate particles in a simulated intestinal fluid. , 2019, Journal of colloid and interface science.

[3]  Xiaopei Wu,et al.  Citric acid enhances the physical properties, cytocompatibility and osteogenesis of magnesium calcium phosphate cement. , 2019, Journal of the mechanical behavior of biomedical materials.

[4]  P. Baglioni,et al.  Tuning the properties of magnesium phosphate-based bone cements: Effect of powder to liquid ratio and aqueous solution concentration. , 2019, Materials science & engineering. C, Materials for biological applications.

[5]  A. Bazzocchi,et al.  Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind, Placebo-Controlled Pilot Study , 2018, Nutrients.

[6]  Jian Yang,et al.  Citrate chemistry and biology for biomaterials design. , 2018, Biomaterials.

[7]  Anita Ignatius,et al.  Bone regeneration capacity of magnesium phosphate cements in a large animal model. , 2018, Acta biomaterialia.

[8]  Jian Yang,et al.  In vitro cytocompatibility evaluation of poly(octamethylene citrate) monomers toward their use in orthopedic regenerative engineering , 2018, Bioactive materials.

[9]  L. Drago,et al.  Recent Evidence on Bioactive Glass Antimicrobial and Antibiofilm Activity: A Mini-Review , 2018, Materials.

[10]  Huan Zhou,et al.  Magnesium-based bioceramics in orthopedic applications. , 2018, Acta biomaterialia.

[11]  Keishi Kiminami,et al.  Effects of Adding Polysaccharides and Citric Acid into Sodium Dihydrogen Phosphate Mixing Solution on the Material Properties of Gelatin-Hybridized Calcium-Phosphate Cement , 2017, Materials.

[12]  N. Baldini,et al.  Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss , 2017, PloS one.

[13]  W. Kołodziejski,et al.  Convenient UV-spectrophotometric determination of citrates in aqueous solutions with applications in the pharmaceutical analysis of oral electrolyte formulations , 2017, Journal of food and drug analysis.

[14]  S. Avnet,et al.  Osteoclast differentiation from human blood precursors on biomimetic calcium-phosphate substrates. , 2017, Acta biomaterialia.

[15]  Prashant N. Kumta,et al.  Magnesium Phosphate Cement Systems for Hard Tissue Applications: A Review. , 2016, ACS biomaterials science & engineering.

[16]  Pamela Habibovic,et al.  Calcium phosphates in biomedical applications: materials for the future? , 2016 .

[17]  A. Schilling,et al.  Effects of extracellular magnesium extract on the proliferation and differentiation of human osteoblasts and osteoclasts in coculture. , 2015, Acta biomaterialia.

[18]  R. T. Tran,et al.  Citrate-Based Biomaterials and Their Applications in Regenerative Engineering. , 2015, Annual review of materials research.

[19]  P. Kwan Osteoporosis: From osteoscience to neuroscience and beyond , 2015, Mechanisms of Ageing and Development.

[20]  A. Rouff,et al.  An investigation of the thermal behavior of magnesium ammonium phosphate hexahydrate , 2015, Journal of Thermal Analysis and Calorimetry.

[21]  S. Lanham-New,et al.  The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis , 2015, Osteoporosis International.

[22]  R. T. Tran,et al.  Synthesis and characterization of biomimetic citrate-based biodegradable composites. , 2014, Journal of biomedical materials research. Part A.

[23]  A. Ignatius,et al.  Control of in vivo mineral bone cement degradation. , 2014, Acta biomaterialia.

[24]  L. Olcay,et al.  Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels. , 2014, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[25]  C. Sfeir,et al.  Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. , 2014, Acta biomaterialia.

[26]  J. Skepper,et al.  Citrate bridges between mineral platelets in bone , 2014, Proceedings of the National Academy of Sciences.

[27]  F. Tancret,et al.  Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. , 2014, Acta biomaterialia.

[28]  W. Bowles,et al.  Antimicrobial properties and dentin bonding strength of magnesium phosphate cements. , 2013, Acta biomaterialia.

[29]  H. Hulter,et al.  Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. , 2013, The Journal of clinical endocrinology and metabolism.

[30]  Sergey V. Dorozhkin,et al.  Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes and Putties , 2012 .

[31]  J. Planell,et al.  Injectable calcium-phosphate-based composites for skeletal bone treatments , 2012, Biomedical materials.

[32]  Y. Kawaguchi,et al.  Vertebroplasty Using Calcium Phosphate Cement for Osteoporotic Vertebral Fractures: Study of Outcomes at a Minimum Follow-up of Two Years , 2012, Asian spine journal.

[33]  G. Arepally,et al.  Anticoagulation techniques in apheresis: From heparin to citrate and beyond , 2012, Journal of clinical apheresis.

[34]  Uwe Gbureck,et al.  Injectability and mechanical properties of magnesium phosphate cements , 2011, Journal of materials science. Materials in medicine.

[35]  S. Mallapragada,et al.  Biomimetic self-assembling copolymer-hydroxyapatite nanocomposites with the nanocrystal size controlled by citrate , 2011 .

[36]  Maria-Pau Ginebra,et al.  Novel magnesium phosphate cements with high early strength and antibacterial properties. , 2011, Acta biomaterialia.

[37]  L. Grover,et al.  Effect of cold-setting calcium- and magnesium phosphate matrices on protein expression in osteoblastic cells. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[38]  T. Arnett Acidosis, hypoxia and bone. , 2010, Archives of biochemistry and biophysics.

[39]  Uwe Gbureck,et al.  Low temperature fabrication of magnesium phosphate cement scaffolds by 3D powder printing , 2010, Journal of materials science. Materials in medicine.

[40]  Changsheng Liu,et al.  Evaluation of inherent toxicology and biocompatibility of magnesium phosphate bone cement. , 2010, Colloids and surfaces. B, Biointerfaces.

[41]  S. Dorozhkin,et al.  Nanosized and nanocrystalline calcium orthophosphates. , 2010, Acta biomaterialia.

[42]  A. Litsky,et al.  Influence of bone cements on bone-screw interfaces in the third metacarpal and third metatarsal bones of horses. , 2009, American journal of veterinary research.

[43]  H. Gruber,et al.  Skeletal and Hormonal Effects of Magnesium Deficiency , 2009, Journal of the American College of Nutrition.

[44]  Changsheng Liu,et al.  Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration. , 2008, Acta biomaterialia.

[45]  David Kovacevic,et al.  Augmentation of Tendon-to-Bone Healing with a Magnesium-Based Bone Adhesive , 2008, The American journal of sports medicine.

[46]  E. Schneider,et al.  Long‐term reaction to bone cement in osteoporotic bone: new bone formation in vertebral bodies after vertebroplasty , 2008, Journal of anatomy.

[47]  D S Mavinic,et al.  Thermal decomposition of struvite and its phase transition. , 2008, Chemosphere.

[48]  P. Schlesinger,et al.  Calcium signalling and calcium transport in bone disease. , 2007, Sub-cellular biochemistry.

[49]  L. Grover,et al.  Ionic modification of calcium phosphate cement viscosity. Part I: hypodermic injection and strength improvement of apatite cement. , 2004, Biomaterials.

[50]  L. Grover,et al.  Ionic modification of calcium phosphate cement viscosity. Part II: hypodermic injection and strength improvement of brushite cement. , 2004, Biomaterials.

[51]  E. Fernández,et al.  Kinetic study of citric acid influence on calcium phosphate bone cements as water-reducing agent. , 2002, Journal of biomedical materials research.

[52]  L. Uhl,et al.  Unexpected citrate toxicity and severe hypocalcemia during apheresis , 1997, Transfusion.

[53]  J. Sharp,et al.  Phase changes on heating ammonium magnesium phosphate hydrates , 1988 .

[54]  J. Glusker Citrate conformation and chelation: enzymic implications , 1980 .