Presence Of Hydroxyapatite Research Articles

Fabrication of multifunctional alginate microspheres containing hydroxyapatite powder for simultaneous cell and drug delivery.

Novel alginate-hydroxyapatite hybrid microspheres were developed for simultaneous delivery of drugs and cells as a multifunctional bone substitute for osteoporotic bone tissue regeneration. The microspheres were used to enhance osteogenesis and to carry and deliver quercetin, a representative phytoestrogen that controls bone tissue regeneration metabolism in osteoporosis patients, through sustained release over a long period. To overcome quercetin’s hydrophobicity and low solubility in aqueous environments, we added it to the surface of hydroxyapatite (HAp) nanoparticles before mixing them with an alginate solution. The homogeneous distribution of the HAp nanoparticles in the alginate solution was essential for preventing nozzle clogging and achieving successfully fabricated hybrid microspheres. To this end, a 3D ultrasonic treatment was applied. Electrostatic microencapsulation was then used to fabricate hybrid alginate-HAp microspheres containing quercetin and cells. The microspheres were approximately 290.7 ± 42.5 μm (aspect ratio of 1). The sustained release of quercetin was confirmed during a test period of 20 weeks. The cells in the hybrid microspheres maintained good cell viability during the entire testing period, and their osteogenic differentiation behavior was boosted by the presence of HAp. Thus, osteogenic differentiation could be greatly improved by adding quercetin. These novel multi-biofunctional hybrid microspheres have great potential for the regeneration of osteoporotic bone tissue at indeterminate defect sites.

Tunable Hydroxyapatite/Magnetite Nanohybrids with Preserved Magnetic Properties

AbstractMagnetic nanoparticles (MNPs) have been extensively investigated in a wide range of biomedical applications. Controlled coating of the MNPs is commonly utilized to protect and maintain their magnetic properties and to improve their biocompatibility, hydrophilicity, colloidal stability and overall biodistribution. Hydroxyapatite (HAp), a highly biocompatible material, is considered for the functionalization of MNPs. In this study, two simple chemical approaches are used to prepare nanohybrid MNPs‐on‐HAp and HAp‐on‐MNPs composites. The effect of heat treatment on the phase composition, morphology, and magnetic properties of both types of magnetic composites is extensively evaluated. In the presence of HAp, MNPs are segregated onto their surfaces and their transformation to hematite upon heat treatment is delayed. On the other hand, needle‐shaped HAp nanocrystallites preferentially grow onto the hydroxylated MNPs surfaces, leading to a synergistic enhancement in the magnetic properties of the produced nanocomposites, with preserved magnetic properties. Compared with a saturation magnetization (Ms) value of 80 emu g−1 of pure MNPs, a MNPs‐on HAp nanohybrid shows a maximum of 14 emu g−1, while nanohybrids based on HAp‐on‐MNPs show Ms values in the range of 43–78 emu g−1. These findings demonstrate the ability to fine‐tune the magnetic properties of the HAp/MNPs nanohybrids via optimizing their processing conditions.

Development and properties of UV‐cured poly (propylene fumarate)/hydroxyapatite composites coatings as potential application for bone adhesive tape

AbstractAs an alternative for polymethyl methacrylate, poly (propylene fumarate) (PPF) has been considered as injectable and biodegradable bone cement; therefore, its mechanical and degradation properties are particularly important. As an environmentally friendly PPF‐based copolymer, which is reinforced by hydroxyapatite, was studied for the properties of the composite. The composites were investigated by evaluating their mechanical properties, hydrophilicity, in vitro degradability, and cytocompatibility. Furthermore, via applying MC3T3‐E1 cells, their cell interaction, including adhesion, proliferation, and in vitro cytotoxicity assay, were assessed. The composite reinforced with 3 wt% hydroxyapatite showed a higher lap‐shear strength (0.71 MPa) and bonding strength (5.24 MPa), a maximum compression strength at fracture (92.44 MPa), and compression strength at yield (35.44 MPa), respectively. Also, mechanical strength, hydrophilicity, and in vitro degradation of composites were enhanced in the presence of hydroxyapatite. In this condition, after a period of immersion (52 weeks) in PBS, the weight loss and degradation rate of composites were found to increased. Cell culture tests indicated that the composite was nontoxic and meaningfully facilitated cell attachment and proliferation. Accordingly, controllable strength and degradation of the composite, along with its proven biocompatibility, make the composite a candidate for the treatment of comminuted fractures.

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for 230U Targeted α-Therapy.

Uranium-230 is an α-emitting radionuclide with favorable properties for use in targeted α-therapy (TAT), a type of nuclear medicine that harnesses α particles to eradicate cancer cells. To successfully implement this radionuclide for TAT, a bifunctional chelator that can stably bind uranium in vivo is required. To address this need, we investigated the acyclic ligands H2dedpa, H2CHXdedpa, H2hox, and H2CHXhox as uranium chelators. The stability constants of these ligands with UO22+ were measured via spectrophotometric titrations, revealing log βML values that are greater than 18 and 26 for the "pa" and "hox" chelators, respectively, signifying that the resulting complexes are exceedingly stable. In addition, the UO22+ complexes were structurally characterized by NMR spectroscopy and X-ray crystallography. Crystallographic studies reveal that all six donor atoms of the four ligands span the equatorial plane of the UO22+ ion, giving rise to coordinatively saturated complexes that exclude solvent molecules. To further understand the enhanced thermodynamic stabilities of the "hox" chelators over the "pa" chelators, density functional theory (DFT) calculations were employed. The use of the quantum theory of atoms in molecules revealed that the extent of covalency between all four ligands and UO22+ was similar. Analysis of the DFT-computed ligand strain energy suggested that this factor was the major driving force for the higher thermodynamic stability of the "hox" ligands. To assess the suitability of these ligands for use with 230U TAT in vivo, their kinetic stabilities were probed by challenging the UO22+ complexes with the bone model hydroxyapatite (HAP) and human plasma. All four complexes were >95% stable in human plasma for 14 days, whereas in the presence of HAP, only the complexes of H2CHXdedpa and H2hox remained >80% intact over the same period. As a final validation of the suitability of these ligands for radiotherapy applications, the in vivo biodistribution of their UO22+ complexes was determined in mice in comparison to unchelated [UO2(NO3)2]. In contrast to [UO2(NO3)2], which displays significant bone uptake, all four ligand complexes do not accumulate in the skeletal system, indicating that they remain stable in vivo. Collectively, these studies suggest that the equatorial-spanning ligands H2dedpa, H2CHXdedpa, H2hox, and H2CHXhox are highly promising candidates for use in 230U TAT.

Development of sodium alginate-pectin/TiO2 nanocomposites: Antibacterial and bioactivity investigations

In this research, sodium alginate-pectin composite (ALG-PEC CS) and nanocomposites (NCs) films with 0.5, 1, and 2 wt% TiO2 nanoparticles (NPs) were prepared using CaCl2 and glutaraldehyde (Glu) as cross-linkers. The cross-linking produces rigid scaffolds for sedimentation of hydroxyapatite (HA), it can also decrease solubility in water and simulated body fluid (SBF) solution to 10% or less. The increase of the adsorbed water and SBF extends the pores and consequently the surface area for HA growth. Bioactive ability was confirmed via HA's presence on the all films. It was revealed that the film containing 2 wt% TiO2 NPs had the best bioactivity without any in vitro cytotoxicity on MG-63 cell line and the best antibacterial performance against Staphylococcus aureus, and after 1 h all the bacteria were killed.

Mineralized Polyvinyl Alcohol/Sodium Alginate Hydrogels Incorporating Cellulose Nanofibrils for Bone and Wound Healing.

Bio sustainable hydrogels including tunable morphological and/or chemical cues currently offer a valid strategy of designing innovative systems to enhance healing/regeneration processes of damaged tissue areas. In this work, TEMPO-oxidized cellulose nanofibrils (T-CNFs) were embedded in alginate (Alg) and polyvinyl alcohol (PVA) solution to form a stable mineralized hydrogel. A calcium chloride reaction was optimized to trigger a crosslinking reaction of polymer chains and mutually promote in situ mineralization of calcium phosphates. FTIR, XRD, SEM/EDAX, and TEM were assessed to investigate the morphological, chemical, and physical properties of different mineralized hybrid hydrogels, confirming differences in the deposited crystalline nanostructures, i.e., dicalcium phosphate dehydrate (DCPDH) and hydroxyapatite, respectively, as a function of applied pH conditions (i.e., pH 4 or 8). Moreover, in vitro tests, in the presence of HFB-4 and HSF skin cells, confirmed a low cytotoxicity of the mineralized hybrid hydrogels, and also highlighted a significant increase in cell viability via MTT tests, preferentially, for the low concentration, crosslinked Alg/PVA/calcium phosphate hybrid materials (<1 mg/mL) in the presence of hydroxyapatite. These preliminary results suggest a promising use of mineralized hybrid hydrogels based on Alg/PVA/T-CNFs for bone and wound healing applications.

In vitro biocompatiability and mechanical properties of bone adhesive tape composite based on poly(butyl fumarate)/poly(propylene fumarate)-diacrylate networks

Polyfumarate has been considered as injectable and biodegradable bone cement. However, its mechanical and degradation properties are particularly important. Therefore, the current study aimed to develop the properties by compositing poly (butyl fumarate)-based networks with hydroxyapatite nano-powders. In this regard, the poly (butyl fumarate) (PBF) matrix composite was compared with different components by evaluating their composition, mechanical properties, hydrophilicity, and biodegradability. Furthermore, their bioactivity in the phosphate-buffered saline (PBS) and, via applying mouse embryo osteoblast precursor cells (MC3T3-E1), their cell interaction, including adhesion, proliferation, and in vitro cytotoxicity assay, were assessed. The addition of hydroxyapatite improved the mechanical strength and modulus of PBF matrix composite. The composite reinforced with 3 wt% hydroxyapatite showed a higher lap-shear strength (1.68 MPa) and bonding strength (4.30 MPa), a maximum compression strength at fracture (95.18 MPa), modulus (925.29 MPa), and compression strength at yield (31.43 MPa), respectively. Also, hydrophilicity and in vitro degradation of the composite were enhanced in the presence of hydroxyapatite. In this condition, after a period of immersion (52 weeks) in PBS, the weight loss rate, and degradation rate of the composite increased. The composite proliferation, adhesion, and toxicity of MC3T3-E1 cells improved in comparison to the PBF matrix composite. Accordingly, controllable strength and degradation of the composite, along with its proven biocompatibility, make the composite a candidate for the treatment of comminuted fractures.

Investigations on the Influence of Collagen Type on Physicochemical Properties of PVP/PVA Composites Enriched with Hydroxyapatite Developed for Biomedical Applications.

Nowadays, a great attention is directed into development of innovative multifunctional composites which may support bone tissue regeneration. This may be achieved by combining collagen and hydroxyapatite showing bioactivity, osteoconductivity and osteoinductivity with such biocompatible polymers as polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) (PVA). Here PVA/PVP-based composites modified with hydroxyapatite (HAp, 10 wt.%) and collagen (30 wt.%) were obtained via UV radiation while two types of collagen were used (fish and bovine) and crosslinking agents differing in the average molecular weight. Next, their chemical structure was characterized using Fourier transform infrared (FT-IR) spectroscopy, roughness of their surfaces was determined using a stylus contact profilometer while their wettability was evaluated by a sessile drop method followed by the measurements of their surface free energy. Subsequently, swelling properties of composites were verified in simulated physiological liquids as well as the behavior of composites in these liquids by pH measurements. It was proved that collagen-modified composites showed higher swelling ability (even 25% more) compared to unmodified ones, surface roughness, biocompatibility towards simulated physiological liquids and hydrophilicity (contact angles lower than 90°). Considering physicochemical properties of developed materials and a possibility of the preparation of their various shapes and sizes, it may be concluded that developed materials showed great application potential for biomedical use, e.g., as materials filling bone defects supporting their treatments and promoting bone tissue regeneration due to the presence of hydroxyapatite with osteoinductive and osteoconductive properties.

Ferrihydrite reduces the bioavailability of copper and cadmium and phosphorus release risk in hydroxyapatite amended soil

Hydroxyapatite (HAP) can effectively decrease bioavailability of trace metals in soils, but the phosphorus (P) release risk was not fully known. In this study, the impacts of ferrihydrite (FH) on passivation of copper (Cu) and cadmium (Cd) and P release risk in soil amended by HAP were investigated under flooding conditions. Results showed that the combinations of HAP and FH increased soil pore water pH by 0.74–2.24 units and reduced phosphate by 71.1–99.5% than single HAP. Soil pore water Cu2+ and Cd2+ in HAP plus 5% FH treated soils were decreased by 96.8–98.6% and 86.6–98.6% than those of single HAP. The combinations of HAP and FH significantly decreased CaCl2 extractable Cu and Cd by 55.9–99% and 13–72.2%, respectively. Moreover, the combinations of HAP and FH significantly decreased exchangeable Cu 47.1–91.5%, but only FH5 decreased exchangeable Cd by 69.4% than the single HAP. Amorphous iron oxide in FH treated soils was 4.06–20 times higher than control, but some of them were transformed into crystalline iron oxide after 42-d flooding incubation. The FH significantly decreased soil labile P by 42.8–78.8% in the presence of HAP and increased stable P by 23.1–33.5% than the single HAP. This study suggested that the addition of FH can not only promote the passivation of HAP on Cu and Cd in the soil, but also reduce the P release risk. Overall, this study highlighted the potential value of the combination of HAP and FH in the passivation of Cu and Cd contaminated soils.

Critical Role of Silicon in Directing the Bio-inspired Mineralization of Gelatin in the Presence of Hydroxyapatite

Critical Role of Silicon in Directing the Bio-inspired Mineralization of Gelatin in the Presence of Hydroxyapatite

Electrochemical and biological behaviour of near β Titanium alloy for biomedical implant applications

Pulsed laser deposition technique (PLD) is one of the methods to coat hydroxyapatite on near beta titanium alloys (Ti-13Nb-13Zr) implants which are used in orthopaedics and dentistry applications. In this study, Hydroxyapatite (HA) ceramics in the form of calcium phosphate (Cap) were deposited on nearβ Titanium alloys (Ti-13Nb-13Zr) by the pulsed laser deposition method. The coated thin film was characterised by X-ray diffraction (XRD), scanning electron microscopy (SEM) with Energy dispersive spectroscopy (EDS) and atomic microscopy (AFM). The corrosion studies were carried out coated and uncoated samples using potentiodynamic polarisation studies in simulated body fluid (Hanks’ solution). The bioactivity of the Hap-coated samples on nearβ Titanium alloys was evaluated by immersing them in simulated body fluid (SBF) for nine days. XRD and EDS analysis confirmed the presence of hydroxyapatite. The corrosion studies showed that the treated samples have better corrosion resistance compared to uncoated substrates. The formation of apatite on treated samples revealed the bioactivity of the Hap-coated substrates. HA-coated nearβ Titanium alloys provide higher corrosion protection than substrates, which can be used for biomedical implant applications.

Effect of Asian Sea Bass (Lates calcarifer) Bio-calcium in Combination with Different Calcium Salts on Gel Properties of Threadfin Bream Surimi

ABSTRACT Impact of bio-calcium from bone (FBC) of Asian sea bass (Lates calcarifer) at 8% (w/w) without and with calcium chloride (CC) or calcium lactate (CL) at different levels (0.1–0.6%, w/w) on gel characteristics of threadfin bream surimi was studied. Surimi added with 8% FBC (BC-8) showed the highest B-F with higher whiteness and water holding capacity (P < .05). When surimi gel containing 8% FBC was incorporated with CC or CL at either 0.4 or 0.6%, the highest B-F, the lowest expressible moisture content and higher whiteness was obtained for gel added with 8% FBC together with 0.6% CL (BC-CL-0.6) (P < .05) and had elastic texture as confirmed by the highest Gʹ and denser microstructure. FTIR spectra confirmed the presence of hydroxyapatite in BC-8 and BC-CL-0.6 samples. Thus, the addition of 8% FBC and 0.6% calcium lactate augmented the gel properties and consumer acceptability of threadfin bream surimi.

Bis[2-(Methacryloyloxy) Ethyl] Phosphate as a Primer for Enamel and Dentine

Dental resin composites are commonly used in the restorative management of teeth via adhesive bonding, which has evolved significantly over the past few decades. Although current self-etch bonding systems decrease the number of clinical steps, the acidic functional monomers employed exhibit a limited extent of demineralization of enamel in comparison to phosphoric acid etchants, and the resultant superficial ionic interactions are prone to hydrolysis. This study evaluates the etching of primers constituted with bis[2-(methacryloyloxy) ethyl] phosphate (BMEP) of dental hard tissue, interfacial characteristics, and inhibition of endogenous enzymes. We examine the incorporation of 2 concentrations of BMEP in the formulation of experimental primers used with a hydrophobic adhesive to constitute a 2-step self-etching bonding system and compare to a commercial 10–methacryloyloxydecyl dihydrogen phosphate (10-MDP)–containing system. The interaction of the primer with enamel and dentine was characterized using scanning electron, confocal laser scanning, and Raman microscopy while the polymerization reaction between the BMEP primers and hydroxyapatite was evaluated by Fourier-transform infrared spectroscopy. The inhibitory effect against matrix metalloproteinase (MMP) enzymes of these primers was studied and percentage of inhibition analyzed using 1-way analysis of variance and Tukey’s post hoc test (P < 0.05). Results of the scanning electron microscopy micrographs demonstrated potent etching of both enamel and dentine with the formation of longer resin tags with BMEP primers compared to the 10-MDP–based system. The BMEP polymerized on interaction with pure hydroxyapatite in the dark, while the 10-MDP primer exhibited the formation of salts. Furthermore, BMEP primers were able to inhibit MMP activity in a dose-dependent manner. BMEP could be used as a self-etching primer on enamel and dentine, and the high degree of polymerization in the presence of hydroxyapatite can contribute to an increased quality of the resin polymer network, prompting resistance to gelatinolytic and collagenolytic degradation.

Hybrid Methods Combining Computational and Experimental Measurements for the Uptake of Eriochrome Black T Dye Utilising Fish Scales

ABSTRACT The current work describes the removal efficiency of a hazardous azo dye such as Eriochrome Black T from aqueous solution using Sardina fish scales as an inexpensive biosorbent which the characterisation results indicate the presence of hydroxyapatite and collagen fibres. Various parameters that can influence the uptake, like contact time, pH, biosorbent dose were investigated, and the optimal experimental removal efficiency was found at acidic pH. The adsorption behaviour of EBT dye on both collagen and hydroxyapatite (HDA) was highlighted using Metropolis Monte Carlo (MC), radial distribution function (RDF), the density functional theory (DFT), and the electrostatic potential surface (ESP) calculations. The findings result in evidence that the EBT dye presents more capabilityto be adsorbed on the collagen than on the HDA surface mainly in an acidic medium. A good agreement between experimental and theoretical conclusions is obtained. The results illustrated that the experimental data were well followed by the pseudo-second-order kinetic and Freundlich isotherm models. Thermodynamic parameters were determined and show that the biosorption of dye was endothermic.

Silicification of Amine-Epoxide Cationic Microgels: An In Vitro Investigation.

Herein, the applicability of an unconventional, non-vinylic type of amine-epoxide microgels (MGs) to promote silica deposition from tetraethyl orthosilicate (TEOS) was investigated. Simply mixing MGs with TEOS in water at 25 °C resulted in the formation of hybrid silica-MG particles (sMGs) as a function of silicification time. The sMGs were cationic with thermal-sensitive swelling capability. Extending silicification time to 24 h was shown to increase silica content to 43%. Besides, the sMGs became structurally more rigid to resist drying-induced deformation and exhibited a rugged surface texture. Mechanistically, the aminated nature of the MGs was proved beneficial for the success of their silicification, fulfilling dual functions of the catalyst for TEOS hydrolysis and template for silica deposition. Through electrostatic adsorption, the sMGs provided a facile yet robust option for surface modifications toward bone-related applications. Surface-induced mineralization in simulated biological fluids was observed with sMG-immobilized surfaces, where the presence of hydroxyapatite was characterized in the deposited apatite. In vitro MC3T3-E1 pre-osteoblast cell studies showed that cell adhesion, morphology, and proliferation could be influenced by both sMG types and their adsorption density. Of particular interest is the finding of cells exhibiting elongated and greatly polarized morphology on the surface with high adsorption density of sMGs of 43% silica. It was postulated that the rugged appearance of such sMGs could have presented a hierarchically structured surface toward cells, an interesting aspect to be further exploited for the engineering of cell-surface interactions.

Mineral Characterization in Human Body: A Dual Energy Approach

Kidney and uteric stones are a common cause of pain and disturbance in numerous people worldwide, as they tend to reappear. There are several studies investigating the association of urolithiasis and nephrolithiasis with atherosclerosis, as patients suffering from the former diseases were found to have been diagnosed with atherosclerotic plaques. Hydroxyapatite and calcium oxalate are the most common mineral crystals found in both kidney/uteric stones and atherosclerotic plaques’ calcifications. Even though for stones smaller than 5 mm surgery is not recommended, the knowledge of the stone composition is an important tool for the physician in order to provide better treatment for the patient. The mineral crystal characterization of atherosclerotic plaques’ calcifications smaller than 3 mm (spotty calcifications) will assist the physician to limit the possibility of myocardial infraction and stroke, as the presence of hydroxyapatite indicates possible plaque rapture. To this aim, a dual energy (DE) X-ray method was developed in this work. The calcium/phosphorus mass ratio (mCa/mP) was determined through analytical simulations and the results were verified experimentally. Both monoenergetic and polyenergetic simulation studies were implemented for hydroxyapatite, calcium carbonate and calcium oxalate with thicknesses ranging from 0.50 to 3.00 mm, at 100 μm increments, to obtain the optimized irradiation conditions. The experimental verification of the proposed method was performed using an X-ray tube combined with a high resolution complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) detector. The Mann–Whitney U test indicated that statistically significant differences were found between the different types of minerals examined for thicknesses of 0.70 mm or higher.

Remineralization of dentin induced by a compound of polyamide-amine and chlorhexidine in a resin dentin bonding microenvironment.

BackgroundThe purpose of this study was to investigate the effect of a complex of polyamide-amine dendrimer (PAMAM) and chlorhexidine gluconate (CG) on remineralization of dentin in an artificial simulated resin dentin bonding microenvironment.MethodsThe structure of this complex was characterized by FT-IR. Twelve standard dentin samples were randomly divided into four treatment fluid groups namely a PAMAM group, CG group, PAMAM + CG group, and deionized water group. A microenvironmental mineralization model was established in vitro with 50 µm gap width between resin and dentin. The dentin surface was observed by a scanning electron microscope (SEM), and the chemical structure of the surface was analyzed by X-ray energy spectrum (EDS), X-ray diffraction (XRD), and laser Raman spectroscopy.ResultsSEM showed the density of dentinal tubules exposed in the PAMAM group decreased after a 14-day immersion, with corn rod-shaped crystal structures gathered around the tubules. In addition, visible mineralization occurred in partial areas of the CG group, rod-shaped crystals and in comparison, dentinal tubules in the PAMAM + CG group were almost completely covered by flaky crystal structures. Raman spectrum analysis showed that crystals formed by PAMAM, CG, and PAMAM + CG solution all had strong phosphate characteristic peaks, indicating the presence of hydroxyapatite (HA), that of the PAMAM + CG group was the strongest. The EDS results showed that the Ca and P levels of the PAMAM group and the CG group were slightly higher than those of the deionized water group, while PAMAM + CG group significantly higher than the others, Ca/P value approaching 1.67. The results of XRD showed the characteristic peaks of hydroxyapatite detected by the PAMAM + CG group at 2θ=26.0 (002), 2θ=32.0 (211), and 2θ=33.0 (112) were high and sharp, with a few diffraction line burrs indicating it had high crystallinity and purity. The Scherrer equation results showed that the appearance and size of the grains formed by the PAMAM + CG group were basically consistent with those of healthy dentin.ConclusionsAltogether, the compound of polyamide-amine dendrimer and chlorhexidine could induce the remineralization of human dentin in a resin dentin bonding microenvironment with a gap of 50 µm to form a crystal structure similar to dentin hydroxyapatite.

68Ga]Ga-THP-Pam: A Bisphosphonate PET Tracer with Facile Radiolabeling and Broad Calcium Mineral Affinity.

Calcium minerals such as hydroxyapatite (HAp) can be detected noninvasively in vivo using nuclear imaging agents such as [18F]NaF (available from cyclotrons), for positron emission tomography (PET) and 99mTc-radiolabeled bisphosphonates (BP; available from 99mTc generators for single photon emission computed tomography (SPECT) or scintigraphy). These two types of imaging agents allow detection of bone metastases (based on the presence of HAp) and vascular calcification lesions (that contain HAp and other calcium minerals). With the aim of developing a cyclotron-independent PET radiotracer for these lesions, with broad calcium mineral affinity and simple one-step radiolabeling, we developed [68Ga]Ga-THP-Pam. Radiolabeling with 68Ga is achieved using a mild single-step kit (5 min, room temperature, pH 7) to high radiochemical yield and purity (>95%). NMR studies demonstrate that Ga binds via the THP chelator, leaving the BP free to bind to its biological target. [68Ga]Ga-THP-Pam shows high stability in human serum. The calcium mineral binding of [68Ga]Ga-THP-Pam was compared in vitro to two other 68Ga-BPs which have been successfully evaluated in humans, [68Ga]Ga-NO2APBP and [68Ga]Ga-BPAMD, as well as [18F]NaF. Interestingly, we found that all 68Ga-BPs have a high affinity for a broad range of calcium minerals implicated in vascular calcification disease, while [18F]NaF is selective for HAp. Using healthy young mice as a model of metabolically active growing calcium mineral in vivo, we compared the pharmacokinetics and biodistribution of [68Ga]Ga-THP-Pam with [18F]NaF as well as [68Ga]NO2APBP. These studies revealed that [68Ga]Ga-THP-Pam has high in vivo affinity for bone tissue (high bone/muscle and bone/blood ratios) and fast blood clearance (t1/2 < 10 min) comparable to both [68Ga]NO2APBP and [18F]NaF. Overall, [68Ga]Ga-THP-Pam shows high potential for clinical translation as a cyclotron-independent calcium mineral PET radiotracer, with simple and efficient radiochemistry that can be easily implemented in any radiopharmacy.

Effects of hematite on the stabilization of copper, cadmium and phosphorus in a contaminated red soil amended with hydroxyapatite.

Iron (Fe) oxides are intimately coupled with phosphorus and closely associated with the bioavailability of potential toxic elements (PTEs) in soil. Thus, Fe oxides may influence the stabilization of PTEs in contaminated soils amended by phosphorus. To evaluate the effects of hematite (HMT) on the stabilization of PTEs, 1-5% (by weight) of HMT was added into a contaminated red soil amended with hydroxyapatite (HAP) to simulate naturally occurring Fe oxides. The stabilization efficiencies of soil copper (Cu) and cadmium (Cd) amended with HAP in soils with low, moderate, and high content of HMT were assessed after a 60-day incubation. HAP treated the soil with high rate HMT decreased the CaCl2-extractable and acid-soluble fractions of Cu and Cd than that of HAP alone. In particular, CaCl2-extactable Cu and Cd in the soil with 5% HMT amended by HAP were 91-95% and 41-68% lower than those amended with only HAP. High content of HMT in soil could decrease the concentration of labile phosphorus in the presence of HAP, but it did not increase the concentration of NaOH-extractable inorganic phosphorus (the fraction bound to Fe oxides). The concentrations of free and crystalline Fe oxides were significantly increased by adding high dosages of HMT with or without HAP. High content of HMT in soil amended by HAP reduced metal phytotoxicity and uptake by wheat shoots than the soil containing HAP without HMT. The results indicate that HMT can promote Cu and Cd stabilization while decrease labile phosphorus in red soil amended with HAP, suggesting that phosphorus-based amendments combined with Fe oxides can be used to stabilize PTEs in contaminated red soils.

A hepatocellular carcinoma–bone metastasis-on-a-chip model for studying thymoquinone-loaded anticancer nanoparticles

We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma (HCC)–bone metastasis and to analyze the inhibitory effect of an herb-based compound, thymoquinone (TQ), in hindering the migration of liver cancer cells into the bone compartment. The bioreactor consisted of two chambers, one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite (HAp). Above these chambers, a microporous membrane was placed to resemble the vascular barrier, where medium was circulated over the membrane. It was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone chamber. The number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the hydrogel. TQ was then used as a metastasis-controlling agent in both free form and encapsulated nanoparticles, to analyze its suppressing effect on HCC metastasis. Results indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory effect. In summary, HCC–bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process, hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.