Calcium Deficient Hydroxyapatite Nanoparticles Research Articles

Enhanced Mechanical Properties of 3D Printed Nanocomposites Composed of Functionalized Plant-Derived Biopolymers and Calcium-Deficient Hydroxyapatite Nanoparticles

The combination of plant-derived polymer resins and mineral-based nanoparticles into three dimensional (3D) printable, high-performance nanocomposites suggests a means to improve the sustainability profile of rapid prototyping and additive manufacturing. In this work, our previously published nanocomposite biomaterial system of acrylated epoxidized soybean oil (AESO) and polyethylene glycol (PEGDA) diluent composited with calcium-deficient hydroxyapatite (nHA) nanorods was improved by the substitution of AESO with methacrylated AESO (mAESO) and the partial substitution of PEGDA with isosorbide methacrylate (IM). mAESO was used to increase the degree of crosslinking and reduce the ink viscosity. IM was synthesized by reacting the hydroxyl groups on isosorbide with methacrylic anhydride. The effects of partially replacing PEGDA with IM on the rheology and printability of the nanocomposite inks and the mechanical properties of the resulting nanocomposite materials were quantified. These masked stereolithography (mSLA) printed nanocomposites have greatly improved mechanical properties (tensile strength, Young’s modulus, and Mode-I fracture toughness) due to the shift to mAESO and IM. IM greatly improved the tensile fracture strength and Young’s modulus of the nanocomposites by acting as a reactive diluent and as a stiff segment in the polymer system. Dynamic mechanical analysis revealed that the glass transition temperature of the nanocomposite increased due to the addition of IM. However, IM decreased the strain-at–fracture, making the nanocomposites more brittle. This study demonstrates the development of high-performance mAESO-IM-nHA-based novel nanocomposites that can be easily 3D printed using desktop mSLA, suggesting a facile path forward to improved sustainability in rapid prototyping and additive manufacturing using nanocomposites for a broad range of applications.

Calcium deficient hydroxyapatite by precipitation: Continuous process by vortex reactor and semi-batch synthesis

Precipitation of calcium deficient hydroxyapatite nanoparticles in an environmentally benign manner by using only dilute solutions of calcium hydroxide and phosphoric acid without pH adjustment and addition of other chemicals, and water, being the only by-product was investigated by using continuous flow Vortex Reactor (VR) and Semi-Batch Reactor (SBR). The effect of hydrodynamics by changing the Reynolds number of the jets providing residence times of 8.4 ms to 4.37 s for VR, and by changing the stirrer speed between 100 rpm (Re = 2656) and 1000 rpm (Re = 26560) for SBR, on the particle size, particle size distribution, and morphology of the particles was investigated for both systems. It has been shown that it is possible to produce pure phase hydroxyapatite nanoparticles in the desired morphology by changing production system, without resorting to additives. While VR produced rod-like particles with the crystallite size around 4 nm, SBR produced spherical particles with the crystallite size of around 5 nm.

Theranostic Calcium Phosphate Nanoparticles With Potential for Multimodal Imaging and Drug Delivery.

Calcium phosphate (CaP) bioceramics closely resemble the natural human bone, which is a main reason for their popularity as bone substitutes. However, this compositional similarity makes it difficult to distinguish CaPs, especially in particulate form, from native bone by imaging modalities such as X-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI) to monitor the healing progress. External contrast agents can improve the imaging contrast of CaPs but can affect their physicochemical properties and can produce artifacts. In this work, we have attempted to improve the contrast of CaP nanoparticles via ion substitutions for multimodal imaging. Calcium-deficient hydroxyapatite (CDHA) nanoparticles with silver (Ag), gadolinium (Gd), and iron (Fe) substitution were prepared by a microwave-accelerated wet chemical process to improve the contrast in CT, T1 (spin–lattice), and T2 (spin–spin) MRI relaxation modes, respectively. Ag, Gd, and Fe were substituted at 0.25, 0.5, and 0.25 at.%, respectively. The ion-substituted CDHA (ICDHA) was found to be phase pure by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Transmission electron microscopy (TEM) images showed that the ICDHA nanoparticles were platelet shaped and of 52 ± 2 nm length and 6 ± 1 nm width. The ICDHA showed high contrast in X-ray and CT compared to CDHA. The vibrating sample magnetometry (VSM) studies showed the ICDHA to exhibit paramagnetic behavior compared to diamagnetic CDHA, which was further confirmed by improved contrast in T1 and T2 MRI mode. In addition, the in vitro tetracycline drug loading and release was studied to investigate the capability of these nanoparticles for antibiotic drug delivery. It was found that a burst release profile was observed for 24 h with 47–52% tetracycline drug release. The ICDHA nanoparticles also showed in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli due to Ag, which was further enhanced by antibiotic loading. In vitro biocompatibility studies showed that the triple-ion-substituted ICDHA nanoparticles were cytocompatible. Thus, the ion-substituted CDHA nanoparticles can have potential theranostic applications due to their multimodal image contrast, antibacterial activity, and drug delivery potential. Future work will be conducted with actual bone samples in vitro or in animal models.

Tailoring antibiotic release for the treatment of periodontal infrabony defects using bioactive gelatin-alginate/apatite nanocomposite films

Local antibiotic delivery is preferred for treating periodontitis due to the benefits of high local drug concentration and minimal side effects. However, commercial polymeric drug delivery systems lack bioactivity and need additional bone grafting to treat the periodontal bone loss. In the present work, calcium deficient hydroxyapatite (CDHA) nanoparticles incorporated gelatin-alginate (GA) films were developed as antibiotic releasing bone substitutes for treating infrabony periodontal defects. CDHA nanoparticles (<50 nm) were incorporated into GA polymer blend films prepared by solvent casting method. The degradation rate and ease of handling were controlled by optimising the concentration of polymer solution and CDHA. The effect of loading methodology on the drug release was studied by adding the antibiotic tetracycline to a) polymer blend, b) CDHA, c) polymer CDHA solution and d) both CDHA and polymer blend. Tetracycline loading on polymer matrix resulted in nearly 100% burst release while an incomplete release (40%) was observed from tetracycline loaded CDHA. Sustained drug release for 10 days suitable for treating severe periodontal infections was obtained on equal drug distribution between the polymer blend and CDHA. The bioactive CDHA incorporated GA composite films can provide sustained tetracycline release for the treatment of periodontal infections.

Acrylic cement formulations modified with calcium deficient apatite nanoparticles for orthopaedic applications

Polymethyl methacrylate-based bone cements are used worldwide by the orthopaedic surgeons to secure joint implants with the skeleton. However, the clinical use of this cement is accompanied by complications such as exothermic heat produced during the polymerization reaction, lack of bone bonding ability and shrinkage to name a few. In the present work, the effect of incorporation of calcium-deficient hydroxyapatite nanoparticles on the properties of a commercially available orthopaedic bone cement matrix has been investigated. Initial and final setting time of the cement has been found to decrease with calcium-deficient hydroxyapatite nanoparticles addition. The exothermic heat dissipation during the polymerization has been found to significantly decrease with the calcium-deficient hydroxyapatite nanoparticle incorporation in the bone cement. Contact angle study revealed that with the increasing percentage of calcium-deficient hydroxyapatite nanoparticle, the composite cement becomes more hydrophilic. In vitro biomineralization study confirmed the bioactivity of the nanocomposite bone cement with the formation of primary and secondary apatite on the cement surface. Present study suggests that the incorporation of calcium-deficient hydroxyapatite nanoparticle into the orthopaedic bone cements could help to overcome some of the shortcomings of the orthopaedic cement.

Enhanced protein delivery by multi-ion containing eggshell derived apatitic-alginate composite nanocarriers

Eggshell is an attractive natural source of calcium for the synthesis of hydroxyapatite (HA) as it contains minor amounts of biologically relevant elements such as Mg, Sr, and Si. The mineral phase of the human bone is essentially a calcium deficient hydroxyapatite (CDHA) which shows more bioactivities and absorbance than stoichiometric HA does. Hence, we have attempted to develop a protein delivery system based on eggshell derived CDHA (ECDHA) nanoparticles for bone tissue engineering. Nanoparticles with Ca/P molar ratio of 1.67, 1.61 and 1.51 to form CDHAs with compositions covering the properties of stable HA phase (Ca/P=1.67) to degradable tricalcium phosphate (TCP) phase (Ca/P=1.5) were synthesized by microwave-accelerated wet chemical synthesis using eggshell as well as synthetic calcium hydroxide as calcium precursors. The delivery profiles of bovine serum albumin (BSA), a model protein by the nanocarriers, were studied. Both eggshells derived and synthetic CDHA samples showed maximum amount of loading of 57% and 37%, respectively at a Ca/P ratio of 1.51, comparing to stoichiometric HA. ECDHA also showed a much more BSA release (25%) than synthetically derived CDHA (6.5%) did. To further improve the release profile, alginate coating was carried out on CDHA nanoparticles and the BSA release profiles were evaluated. A maximum release of 65% was observed for alginate coated ECDHA at a Ca/P ratio of 1.51 for a period of 2 days. The ECDHA nanoparticle with a Ca/P ratio similar to degradable TCP and with alginate coating seems to be an ideal protein delivery agent.

A novel strategy for preparing nanoporous biphasic calcium phosphate of controlled composition via a modified nanoparticle-assembly method

Biphasic calcium phosphate (BCP) consisting of hydroxyapatite (HAp) and β-tricalcium phosphate is usually prepared by thermal decomposition of calcium-deficient HAp (CDHAp). However, the calcium deficiency and morphology of CDHAp are difficult to manipulate in parallel. In this study, we report a novel strategy for controlling the composition of nanoporous BCP by using only CDHAp nanoparticles with specific properties (Ca/P molar ratio, 1.61; particle size, 50nm) as a building block and by adjusting the calcium deficiency of the nanoparticle-assembled CDHAp (Ca/P molar ratio, 1.50–1.67; pore size, 8nm) with the addition of water-soluble Ca(NO3)2 or (NH4)2HPO4. After thermal treatment at 1000°C, the composition of BCP could be predictably controlled by adjusting the Ca/P ratio of the nanoparticle-assembled CDHAp. Changes in the Ca/P ratio did not significantly affect the surface morphology of BCP, but the grain size (210–300nm) and pore size (140–170nm) tended to increase slightly as the Ca/P ratio decreased. The porosity significantly decreased upon the addition of Ca salts (porosity, 20%) or PO4 salts (porosity, 14%) compared with that of the sample without additives (porosity, 53%). In vitro tests demonstrated enhanced cell adhesion on nanoporous BCP compared with densely sintered pure HAp, and cell differentiation was promoted on the nanoporous pure HAp.

Strontium‐Substituted Calcium Deficient Hydroxyapatite Nanoparticles: Synthesis, Characterization, and Antibacterial Properties

Strontium‐substituted apatites have provoked increased interest in recent years for their beneficial effects on osteoporotic bone treatment and replacement. In this study, rod‐ and acicular‐shaped, strontium‐substituted calcium deficient hydroxyapatite (CDHA) nanoparticles with (Ca + Sr)/P ratio of 1.61 were synthesized via accelerated microwave processing. The X‐ray powder diffraction analysis indicates the synthesized nanoparticles as apatite phase with diffraction patterns similar to those of hydroxyapatite. The hydrodynamic diameter of the particles were observed to be ~200–500 nm and found to increase with strontium substitution along with an increase in the negative zeta potential by dynamic light scattering method, suggesting the particles to be agglomerates in water. The morphology of the nanoparticles was studied using transmission electron microscopy (TEM), where, pure CDHA showed globular and strontium substituted CDHAs showed rod and acicular shape for 5% and 10% Sr substitution, respectively. The average size of the particles in TEM was measured to be 33 nm × 5 nm, 40 nm × 6 nm, and 55 nm × 8 nm (L × W) for pure and strontium‐substituted CDHAs, respectively. Inductively coupled plasma spectroscopy, energy dispersive X‐ray analysis, and Fourier transform infrared spectroscopy further confirm the substitution of strontium and deficiency of calcium in the synthesized nanoparticles. Thermal stability and in vitro solubility of CDHA nanoparticles were observed to increase with strontium substitution. The MTT [3‐(4, 5‐Dimethylthiazole‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide] assay indicate that the substituted nanoparticles are non‐toxic to human periodontal ligament fibroblast (HPDLF) cells. Cell uptake study by fluorescence microscopy using rhodamine‐123 and actin/DAPI stained HPDLF cells show cellular localization of the nCDHA, nSr5CDHA, nSr10CDHA nanoparticles without any adverse effects. The strontium‐substituted CDHAs showed significant antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria by colony count method. The 10% Sr substituted CDHA show the maximum microbial reduction of around 56% for E. coli and 35% for S. aureus with 1 × 105 cells/mL of respective bacterial culture.

SYNTHESIS AND PROPERTIES OF Fe-MODIFIED CALCIUM-DEFICIENT HYDROXYAPATITE NANOCRYSTAL FOR MRI CONTRAST AGENT

In order to achieve for a better magnetic resonance imaging (MRI) contrast agent, the synthesis, degradation and magnetic properties of Fe -modified calcium deficient hydroxyapatite nanoparticles ( Fe -CDHAP, ( Ca , Fe )10-x( HPO 4)x( PO 4)6-x( OH )2-x), which synthesizes using ultrasonic assisted precipitation at low temperature, were investigated. The MRI contrast agent should be stable, biodegradable and also with great magnetism. The synthesized sample demonstrates needle-like morphology with dimension less than 50 nm in width and 300 nm in length under SEM. The structure and crystal deformation were studied by X-ray diffraction (XRD), which show 0.2% shrinkage in cell volume, through the pattern shifting and the lattice parameters calculations. Thermal gravity analysis (TGA) analysis indicated Fe -CDHAP were stable up to 1200°C and confirmed the structure of the Fe -CDHAP, which is stable. Fourier transform infrared spectroscopy (FTIR) assisted to define the influence of iron substitution and gave the hint of internal structure variation on [Formula: see text] sites that reflect on the great amount of phosphate ions release in acidic solution. The methods above prove the structure of Fe -CDHAP and also indicate the effect to [Formula: see text], which is caused by the doping of iron ions. The degradation test confirms the biodegradability of Fe -CDHAP that can degrade faster than CDHAP and also release a great amount of phosphate ions in a short time. The magnetic property of CDHAP and Fe -CDHAP were determined with VSM to and found the transformation of diamagnetic into paramagnetic.

Sol-gel synthesis of FHA / CDHA nanoparticles with a nonstochiometric ratio

The aim of this study was to investigate the sol ge l synthesis of HA/FA nanoparticles and the possible formation of TCP phase or unstoichiometric calcium deficient hydroxyapatite (CDHA) from the precursors with a Ca/P ratio of 1.62. In order to prepare the sol, the solutions of Triethyl phosphite, ammonium fluoride and calcium nitrate in ethanol were used respective ly as P, F and Ca precursors.The crystallinity, par ticle and crystallite size, powder morphology, chemical struc ture and phase analysis were investigated by SEM, X RD, FT-IR and Zeta sizer experiment. A multiphase compound containing hydroxyapatite (HA) and fluoroapatit e (FA) nanoparticles and calcium deficient hudroxyapatite (CDHA) agglomerates was obtained. The size of the crystallites estimated from XRD patterns using Scherrer equation and the crystallinity of HA phase were about 5 nm and 66% respectively. The zeta sizer ex periments for the dispersed particles in its own conditions showed an average size of 98 nm.

Effect of Hydroxyapatite Nanoparticles on Ibuprofen Release from Carboxymethyl-Hexanoyl Chitosan/O-Hexanoyl Chitosan Hydrogel

In order to explore the effect of nanofiller on the regulation of the drug release behavior from microsphere-embedded hydrogel prepared by carboxymethyl-hexanoyl chitosan (HNOCC) and O-hexanoyl chitosan (OHC), the release kinetics was investigated in terms of various amounts of calcium-deficient hydroxyapatite (CDHA) nanoparticles incorporated. HNOCC is a novel chitosan-based hydrophilic matrix with a burst release profile in a highly swollen state. The drug release kinetics of the HNOCC hydrogel can be regulated by incorporation of well-dispersed CDHA nanoparticles. It was found that the release duration of ibuprofen (IBU) from HNOCC was prolonged with increasing amounts of CDHA which acts as a crosslink agent and diffusion barrier. On the contrary, the release duration of the IBU from OHC (hydrophobic phase) was shortened through increasing the CDHA amount over 5%, which is due to the hydrophilic nature of the CDHA nanoparticles destroying the intermolecular hydrophobic interaction and accelerating OHC degradation. Thus, water accessibility and molecular relaxation were enhanced, resulting in a higher release rate. In addition, sustained and sequential release behavior was achieved by embedding the OHC microspheres (hydrophobic phase) into the HNOCC (hydrophilic phase) matrix, which could significantly prolong the release duration of the HNOCC drug-loaded implant.

Influence of the aspect ratio of bioactive nanofillers on rheological behavior of PMMA-based orthopedic materials.

In this investigation, calcium-deficient hydroxyapatite (CDHA) nanocrystals with needle-like geometry were synthesized and incorporated with Poly(methyl methacrylate), PMMA, to form CDHA-PMMA nanocomposites. Rheological behaviors of the PMMA-CDHA melting suspensions were systematically investigated in terms of solid loading and aspect ratio of the CDHA nanoparticles. The maximum solid loadings of nano-CDHA particles with aspect ratios of 7.2, 10.4, and 17 were determined to be 28, 31, and 57%, respectively. An increase in solid concentrations causes pronounced shear-thinning behavior. This result suggests that a strong interaction, including Van der Waals attraction and mechanical interlocking, between the nano-CDHA particles makes the nanocomposite mixture more non-Newtonian. Furthermore, it was found that packing efficiency and yield strength in the suspension were strongly influenced by the aspect ratio, especially above the critical value of 8.8. The obtained critical aspect ratio and solid content provide not only appropriate design in the PMMA-CDHA polymeric suspension for fabrication process but also optimal conditions for the fabrication of orthopedic devices via injection molding or extrusion.