Syntheses of Single-Crystal Apatite Particles with Preferred Orientation to the &lt;i&gt;a&lt;/i&gt;- and &lt;i&gt;c&lt;/i&gt;-Axes as Models of Hard Tissue and Their Applications

Aizawa, Mamoru; Matsuura, Tomokazu; Zhuang, Zhi

doi:10.1248/bpb.b13-00439

Cited by 48 publications

(31 citation statements)

References 54 publications

(57 reference statements)

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“…Larger changes are however observed for the BHAp, which can be associated with the degree of orientation in the a , b- plane, due to the exposure of OH − channels of the c axis, generating a surface with higher electronegativity, increasing their reactivity when exposed to body fluids [9,28,38]. …”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

et al. 2018

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The physicochemical properties and biological behavior of sintered-bovine-derived hydroxyapatite (BHAp) are here reported and compared to commercial synthetic-HAp (CHAp). Dense ceramics were sintered for 2 h and 4 h at 1200 °C to investigate their microstructure–structure–in-vitro behavior relationship for both HAp ceramics. Densification was directly proportional to sintering time, showing a grain coarsening behavior with a greater effect on BHAp. Lattice parameters, crystallite size, cell volume and Ca/P ratio were determined by Rietveld refinement of X-ray diffraction (XRD) patterns using GSAS®. Ionic substitutions (Na+, Mg2+, CO32−) related to BHAp structure were associated with their position changes in the vibrational modes and correlated with the structural parameters obtained from the XRD analysis. Variations in the structural parameters and surface morphology were also evaluated after different soaking periods in simulated body fluid, which is associated with the formation of bone-like apatite layer and thus bioactivity. Mitochondrial activity (MTS) and lactate dehydrogenase (LDH) assays showed that the material released by the ceramics does not induce toxicity after exposure in human fetal osteoblastic (hFOB) cells. Furthermore, no statistically significant differences were found between the HAp obtained from different sources. These results show that BHAp can be used with no restrictions for the same biomedical applications as CHAp.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

et al. 2018

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“…Additionally, most prismatic, ( hk 0) faces display an excess of Ca 2+ ions, as opposed to the basal, (001) plane that displays an excess of OH − and PO 4 3− groups. 32 By binding exclusively to Ca 2+ ions, the surface concentration of BP molecules is expected to be greater on ( hk 0) faces, blocking their growth and promoting the elongation of the particles in the (001) crystallographic direction. JQ1, in contrast, is expected to bind to HAp through electrostatic attraction between the three potentially protonated nitrogen atoms comprising the tetraazacyclopenta[ e ]azulene ring and the triply charged PO 4 3− ions of HAp, exerting an opposite effect on the Ca/P surface molar ratio (Figure 3b).…”

Section: Resultsmentioning

confidence: 99%

Bisphosphonate-Functionalized Hydroxyapatite Nanoparticles for the Delivery of the Bromodomain Inhibitor JQ1 in the Treatment of Osteosarcoma

Mickens

Uskoković

2017

ACS Appl. Mater. Interfaces

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Osteosarcoma (OS) is one of the most common neoplasia among children, and its survival statistics have been stagnating since the combinatorial anticancer therapy triad was first introduced. Here, we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Both additives decreased the crystallinity of HAp, but the effect was more intense for medronate because of its higher affinity for HAp. As the result of PO43−-NH+ binding, JQ1 shielded the surface phosphates of HAp and pushed its surface charge to more positive values, exhibiting the opposite effect from calcium-blocking medronate. In contrast to the faster and more exponential release of JQ1 from monetite, its release from HAp nanoparticles followed a zero-order kinetics, but 98% of the payload was released after 48 h. The apoptotic effect of HAp nanoparticles loaded with JQ1, with medronate and with both JQ1 and medronate, was selective in 2D culture: pronounced against the OS cells and nonexistent against the healthy fibroblasts. While OS cell invasion was significantly inhibited by all of the JQ1-containing HAp formulations, that is, with and without medronate, all of the combinations of the targeting compound, medronate, and the chemotherapeutic, JQ1, delivered using HAp, but not HAp alone, inhibited OS cell migration from the tumor spheroids. JQ1 delivered using HAp had an effect on tumor migration, invasion, and apoptosis even at extremely low, subnanomolar concentrations, at which no effect of JQ1 per se was observed, meaning that this form of delivery could help achieve a multifold increase of this drug’s efficacy. More than 80% of OS cells internalized JQ1-loaded HAp nanoparticles after 24 h of coincubation, suggesting that this augmentation of the activity of JQ1 may be due to the intracellular delivery and sustained release of the drug enabled by HAp. In addition to the reduction of the OS cell viability, the reduction of the migration and invasion radii was observed in OS tumor spheroids challenged with even JQ1-free medronate-functionalized HAp nanoparticles, demonstrating a definite anticancer activity of medronate alone when combined with HAp. The effect of medronate-functionalized JQ1-loaded HAp nanoparticles was most noticeable against OS cells differentiated into an osteoblastic lineage, in which case they surpassed in effect pure JQ1 and medronate-free compositions. The activity of JQ1 was mediated through increased Ezrin expression and decreased RUNX2 expression and was MYC and FOSL1 independent, but these patterns of gene expression changed in cells challenged with the nanoparticulate form of delivery, having been accompanied by the upregulation of RUNX2 and downregulation of Ezrin in OS cells treated with medronate-functionalized JQ1-loaded HAp nanoparticles.

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“…This remains the simplest and most cost-effective method of protein tethering and does not require prior modification of either protein or biomaterial. Physisorption of proteins onto hard materials such as silicas, [34] ceramics, [35] hydroxyapatite, [36] nanocarriers such as carbons and metals [37] and single-walled carbon nanotubes, [38] and inorganic materials in general, [39] has been extensively studied due to its ease and the opportunity to confer cell-reactive properties on otherwise biologically inert materials. Adsorption of celladhesive fibronectin has been found in some studies to yield more bioactive protein than attachment via covalent conjugation, [40] though both the extent of adsorption and the activity of the adsorbed protein vary considerably between hydrophobic and hydrophilic surfaces.…”

Section: Progress Reportmentioning

confidence: 99%

Adding Functions to Biomaterial Surfaces through Protein Incorporation

et al. 2016

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The concept of biomaterials has evolved from one of inert mechanical supports with a long-term, biologically inactive role in the body into complex matrices that exhibit selective cell binding, promote proliferation and matrix production, and may ultimately become replaced by newly generated tissues in vivo. Functionalization of material surfaces with biomolecules is critical to their ability to evade immunorecognition, interact productively with surrounding tissues and extracellular matrix, and avoid bacterial colonization. Antibody molecules and their derived fragments are commonly immobilized on materials to mediate coating with specific cell types in fields such as stent endothelialization and drug delivery. The incorporation of growth factors into biomaterials has found application in promoting and accelerating bone formation in osteogenerative and related applications. Peptides and extracellular matrix proteins can impart biomolecule- and cell-specificities to materials while antimicrobial peptides have found roles in preventing biofilm formation on devices and implants. In this progress report, we detail developments in the use of diverse proteins and peptides to modify the surfaces of hard biomaterials in vivo and in vitro. Chemical approaches to immobilizing active biomolecules are presented, as well as platform technologies for isolation or generation of natural or synthetic molecules suitable for biomaterial functionalization.

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Syntheses of Single-Crystal Apatite Particles with Preferred Orientation to the <i>a</i>- and <i>c</i>-Axes as Models of Hard Tissue and Their Applications

Cited by 48 publications

References 54 publications

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

Synthesis, Characterization and In Vitro Study of Synthetic and Bovine-Derived Hydroxyapatite Ceramics: A Comparison

Bisphosphonate-Functionalized Hydroxyapatite Nanoparticles for the Delivery of the Bromodomain Inhibitor JQ1 in the Treatment of Osteosarcoma

Adding Functions to Biomaterial Surfaces through Protein Incorporation

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