Strontium-Doped Amorphous Calcium Phosphate Porous Microspheres Synthesized through a Microwave-Hydrothermal Method Using Fructose 1,6-Bisphosphate as an Organic Phosphorus Source: Application in Drug Delivery and Enhanced Bone Regeneration.

Nanostructured calcium phosphate porous microspheres are of great potential in drug delivery and bone regeneration due to their large specific surface area, biocompatibility, and similarity to inorganic component of osseous tissue. In this work, strontium (Sr)-doped amorphous calcium phosphate porous microspheres (SrAPMs) were synthesized through a microwave-hydrothermal method using fructose 1,6-bisphosphate trisodium salt as the source of phosphate ions. The SrAPMs showed a mesoporous structure and a relatively high specific area. Compared with the hydroxyapatite nanorods prepared by using Na2HPO4·12H2O as the phosphorus source, the SrAPMs with a higher specific surface area were more effective in drug loading using vancomycin as the antiobiotics of choice and consequently having a higher antibacterial efficiency both on agar plates and in broths. Furthermore, to assess the potential application of SrAPMs in bone defect repair, a novel biomimetic bone tissue-engineering scaffold consisting of collagen (Coll) and SrAPMs was constructed using a freeze-drying fabrication process. Incorporation of the SrAPMs not only improved the mechanical properties, but also enhanced the osteogenesis of rat bone marrow mesenchymal stem cells. The in vivo experiments demonstrated that the SrAPMs/Coll scaffolds remarkably enhanced new bone formation compared with the Coll and APMs/Coll scaffolds in a rat critical-sized calvarial defect model at 8 weeks postimplantation. In summary, SrAPMs developed in this work are promising as antibiotic carriers and may encourage bone formation when combined with collagen.

[1]  Mingguo Ma,et al.  The progress of microwave-assisted hydrothermal method in the synthesis of functional nanomaterials , 2016 .

[2]  F. O'Brien,et al.  Content-Dependent Osteogenic Response of Nanohydroxyapatite: An in Vitro and in Vivo Assessment within Collagen-Based Scaffolds. , 2016, ACS applied materials & interfaces.

[3]  Ying-Jie Zhu,et al.  Magnesium whitlockite hollow microspheres: a comparison of microwave-hydrothermal and conventional hydrothermal syntheses using fructose 1,6-bisphosphate, and application in protein adsorption , 2016 .

[4]  Xianlong Zhang,et al.  Zn/Ag micro-galvanic couples formed on titanium and osseointegration effects in the presence of S. aureus. , 2015, Biomaterials.

[5]  Anna Tampieri,et al.  Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation. , 2015, Biomaterials.

[6]  Gavin Jell,et al.  Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair. , 2015, Biomaterials.

[7]  Changqing Zhang,et al.  Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects. , 2015, Acta biomaterialia.

[8]  Feng Chen,et al.  Microwave-assisted preparation of inorganic nanostructures in liquid phase. , 2014, Chemical reviews.

[9]  Ira Bhatnagar,et al.  In vivo study of chitosan-natural nano hydroxyapatite scaffolds for bone tissue regeneration. , 2014, International journal of biological macromolecules.

[10]  L. Drago,et al.  A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study. , 2014, The bone & joint journal.

[11]  Hong Li,et al.  Composite scaffolds of nano calcium deficient hydroxyapatite/multi-(amino acid) copolymer for bone tissue regeneration , 2014, Journal of Materials Science: Materials in Medicine.

[12]  A. Lode,et al.  A novel strontium(II)-modified calcium phosphate bone cement stimulates human-bone-marrow-derived mesenchymal stem cell proliferation and osteogenic differentiation in vitro. , 2013, Acta biomaterialia.

[13]  J. Janek,et al.  Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats. , 2013, Biomaterials.

[14]  Jing Zhao,et al.  Hydroxyapatite hierarchically nanostructured porous hollow microspheres: rapid, sustainable microwave-hydrothermal synthesis by using creatine phosphate as an organic phosphorus source and application in drug delivery and protein adsorption. , 2013, Chemistry.

[15]  T. Desai,et al.  Effect of calcium phosphate particle shape and size on their antibacterial and osteogenic activity in the delivery of antibiotics in vitro. , 2013, ACS applied materials & interfaces.

[16]  Jiang Chang,et al.  Strontium substituted hydroxyapatite porous microspheres: Surfactant-free hydrothermal synthesis, enhanced biological response and sustained drug release , 2013 .

[17]  Jing Zhao,et al.  Highly stable amorphous calcium phosphate porous nanospheres: microwave-assisted rapid synthesis using ATP as phosphorus source and stabilizer, and their application in anticancer drug delivery. , 2013, Chemistry.

[18]  P. Marie,et al.  Strontium signaling: molecular mechanisms and therapeutic implications in osteoporosis. , 2012, Pharmacology & therapeutics.

[19]  Ying-Jie Zhu,et al.  Hydroxyapatite nanosheet-assembled porous hollow microspheres: DNA-templated hydrothermal synthesis, drug delivery and protein adsorption , 2012 .

[20]  Mingguo Ma.  Hierarchically nanostructured hydroxyapatite: hydrothermal synthesis, morphology control, growth mechanism, and biological activity , 2012, International journal of nanomedicine.

[21]  María Vallet-Regí,et al.  Bioceramics: From Bone Regeneration to Cancer Nanomedicine , 2011, Advanced materials.

[22]  Jaebeom Lee,et al.  Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration. , 2011, Acta biomaterialia.

[23]  Jiang Chang,et al.  Biomimetic hydroxyapatite porous microspheres with co-substituted essential trace elements: Surfactant-free hydrothermal synthesis, enhanced degradation and drug release , 2011 .

[24]  Ying-Jie Zhu,et al.  Calcium phosphate drug nanocarriers with ultrahigh and adjustable drug-loading capacity: One-step synthesis, in situ drug loading and prolonged drug release. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[25]  J. Barralet,et al.  Bioinorganics and biomaterials: bone repair. , 2011, Acta biomaterialia.

[26]  H. Engqvist,et al.  Synthesis and release of trace elements from hollow and porous hydroxyapatite spheres , 2011, Nanotechnology.

[27]  Lintao Cai,et al.  Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling , 2011, Stem cells.

[28]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

[29]  Jiang Chang,et al.  Effects of strontium in modified biomaterials. , 2011, Acta biomaterialia.

[30]  Jiang Chang,et al.  Flower-like hierarchically nanostructured hydroxyapatite hollow spheres: facile preparation and application in anticancer drug cellular delivery. , 2010, Chemistry, an Asian journal.

[31]  Huipin Yuan,et al.  Osteoinductive ceramics as a synthetic alternative to autologous bone grafting , 2010, Proceedings of the National Academy of Sciences.

[32]  Hala Zreiqat,et al.  The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. , 2010, Biomaterials.

[33]  Yin Xiao,et al.  The osteogenic properties of CaP/silk composite scaffolds. , 2010, Biomaterials.

[34]  M. Vallet‐Regí,et al.  Interaction of an ordered mesoporous bioactive glass with osteoblasts, fibroblasts and lymphocytes, demonstrating its biocompatibility as a potential bone graft material. , 2010, Acta biomaterialia.

[35]  Mingguo Ma,et al.  Solvothermal Synthesis and Characterization of Hierarchically Nanostructured Hydroxyapatite Hollow Spheres , 2009 .

[36]  D. Weitz,et al.  Double Emulsion Droplets as Microreactors for Synthesis of Mesoporous Hydroxyapatite , 2009 .

[37]  Kezheng Chen,et al.  Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method , 2009 .

[38]  F. O'Brien,et al.  The effect of dehydrothermal treatment on the mechanical and structural properties of collagen-GAG scaffolds. , 2009, Journal of biomedical materials research. Part A.

[39]  K. Luk,et al.  Strontium Promotes Osteogenic Differentiation of Mesenchymal Stem Cells Through the Ras/MAPK Signaling Pathway , 2009, Cellular Physiology and Biochemistry.

[40]  J. Goldhahn,et al.  Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis. , 2008, Bone.

[41]  E. Brown,et al.  The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation. , 2007, Biochemical pharmacology.

[42]  W. Lu,et al.  Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite. , 2007, Biomaterials.

[43]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[44]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[45]  Jenny Andersson,et al.  Influences of Material Characteristics on Ibuprofen Drug Loading and Release Profiles from Ordered Micro- and Mesoporous Silica Matrices , 2004 .

[46]  R. Baron,et al.  In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. , 2002, European journal of pharmacology.

[47]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[48]  Lingzhou Zhao,et al.  The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates. , 2013, Biomaterials.

[49]  Jin-Woo Park,et al.  Positive modulation of osteogenesis- and osteoclastogenesis-related gene expression with strontium-containing microstructured Ti implants in rabbit cancellous bone. , 2013, Journal of biomedical materials research. Part A.

[50]  Ying-Jie Zhu,et al.  Fructose 1,6-bisphosphate trisodium salt as a new phosphorus source for the rapid microwave synthesis of porous calcium-phosphate microspheres and their application in drug delivery. , 2013, Chemistry, an Asian journal.

[51]  Casey K Chan,et al.  Stem cell homing in musculoskeletal injury. , 2011, Biomaterials.

[52]  J. Feijen,et al.  Cross-linking of dermal sheep collagen using a water-soluble carbodiimide. , 1996, Biomaterials.