Mesoporous Carbonated Hydroxyapatite Research Articles

Effect of swelling agent on pore properties of mesoporous carbonated hydroxyapatite

Mesoporous carbonated hydroxyapatite (CHA) has been seen to be suitable as an adsorbent material due to the proven biocompatibility, bioactivity and chemical stability. However, obtaining the high surface area and desired pore size for mesoporous materials become the main challenge in producing good quality adsorbent materials. Thus, this study aims to investigate the effect of addition of swelling agents on pore properties of mesoporous CHA. Mesoporous CHA was synthesised by precipitation method. Triblock co-polymer, P123 surfactant was used as a soft template to introduce pores within the CHA particles and 1-dodecanethiol as a swelling agent. Two different mixing temperature (60°C and 80°C) were used during the mixing process of P123-calcium solution and 1-dodecanethiol. The effect of different mixing temperature (60°C and 80°C) and various concentration of swelling agent on the phase, morphology and pore characteristics of mesoporous CHA were investigated using various material characterization techniques. Mixing temperature 60°C, produced mesoporous CHA with much higher surface area (92.8 m2/g), larger pore size (22.9 nm) and higher pore volume (0.502 cm2/g) than those produce at 80°C (surface area = 62.7 m2/g, pore size = 2.6 nm and pore volume = 0.105 cm2/g). The highest surface area (146.9 m2/g) of mesoporous CHA was obtained when there was no swelling agent added. However, the pore size of the sample was very small. Therefore, the optimum pore characteristics (surface area = 104.5 m2/g, pore size = 24.4 nm and pore volume = 0.530 cm2/g) of mesoporous CHA was obtained when the swelling agent concentration is 0.6 M and the mixing temperature is 60°C. Both mixing temperature and swelling agent concentration have profound effect on the pore characteristics of mesoporous carbonated hydroxyapatite (CHA).

Antibacterial Ability of Mesoporous Carbonated Hydroxyapatite

Mesoporous carbonated hydroxyapatite (Meso-CHA) is a bioceramic materials that offer good biocompatibility and bioactivity properties that suitable for bone defects or diseases treatment and therapy. Antibacterial study is very important to ensure that materials is biocompatible enough to be used on or inside the human body. The aim of this study is to investigate the antibacterial ability of the Meso-CHA (without addition of antibacterial agents) towards Escherichia coli (E. coli) bacteria. Meso-CHA samples were synthesized using chemical precipitation method where surfactant P-123 was used to introduce pores within nanoparticles structure. X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) analysis proved that pure phase of Meso-CHA was obtained. Synthesized Meso-CHA demonstrated higher pore properties (surface area = 146.92 m2g−1, pore size = 2.35 nm, and pore volume = 0.2437 cm3g−1) compared to commercial HA (surface area = 7.84 m2 g−1, pore size = 2.05 nm, and pore volume = 0.0085 cm3 g−1). The antibacterial study demonstrated that Meso-CHA has low antibacterial properties with Minimum Inhibitory Concentration (MIC) of 200 mg.ml−1 compared to HA. Carbonate ion addition into the Meso-CHA structure does not improve the antibacterial ability of the materials.

Microwave-assisted hydrothermal synthesis of mesoporous carbonated hydroxyapatite with tunable nanoscale characteristics for biomedical applications

Mesoporous carbonated hydroxyapatite (HAp) with different size, shapes, and the specific surface area has received much interest in various biomedical applications. In this study, we reported a rapid microwave-assisted hydrothermal amalgamation of mesoporous carbonated HAp with tunable nanoscale characteristics using organic modifiers such as oxalic acid and sodium dodecyl sulfate (SDS) as a regulator. The synthesized HAp was analyzed to obtain its physiochemical properties using different characterization techniques to figure out its crystallization nature, particle size, phase purity, elemental composition, pore size, pore volume, and particle size distribution. The observed results clearly showed that the mesoporous carbonated HAp with tunable nanoscale characteristics can be achieved through a microwave enabled hydrothermal digester with the aid of organic modifiers. Moreover, it was found that the addition of oxalic acid during the synthesis can make strong interaction with calcium ions which resulted in the HAp along with calcium oxalate phase whereas the addition of SDS leads to pure HAp phase. Oxalic acid-mediated synthesis leads to form loosely agglomerated rod-like mesoporous nanoparticles having 10 nm width and 20–40 nm length with a specific surface area of 89 m2 g−1 while SDS-mediated synthesis leads to form nanorods bearing 20–45 nm of width, and 55–100 nm of length with specific surface area of 48 m2 g−1. In addition, oxalic acid and SDS also help in tuning the pore size and pore volume by making interaction with HAp crystallites during the synthesis process. Thus, oxalic acid and SDS can plays an important role in modifying structural and physiochemical properties of HAp and it can be used to produce mesoporous HAp nanoparticles through microwave enabled hydrothermal digester for different biomedical applications.

Biomimetic hollow mesoporous hydroxyapatite microsphere with controlled morphology, entrapment efficiency and degradability for cancer therapy

Hollow mesoporous carbonated hydroxyapatite microspheres produced via sodium dodecyl sulfate assisted precipitation can target cancer cells through acidic dependent release of loaded CDDP.

Agarose encapsulated mesoporous carbonated hydroxyapatite nanocomposites powder for drug delivery

The powder composites are predominantly used for filling of voids in bone and as drug delivery carrier to prevent the infection or inflammatory reaction in the damaged tissues. The objective of this work was to study the synthesis of agarose encapsulation on carbonated hydroxyapatite powder and their biological and drug delivery properties. Mesoporous, nanosized carbonated hydroxyapatite/agarose (CHAp/agarose) powder composites were prepared by solvothermal method and subsequently calcined to study the physico-chemical changes, if it subjected to thermal exposure. The phase of the as-synthesized powder was CHAp/agarose whereas the calcinated samples were non-stoichiometric HAp. The CHAp/agarose nanorods were of length 10–80nm and width 40–190nm for the samples synthesized at temperatures 120°C (ST120) and 150°C (ST150). The calcination process produced spheres (10–50nm) and rods with reduced size (40–120nm length and 20–30nm width). Composites were partially dissolved in SBF solution followed by exhibited better bioactivity than non-stoichiometric HAp confirmed by gravimetric method. Hemo and biocompatibility remained unaffected by presence of agarose or carbonate in the HAp. Specific surface area of the composites was high and exhibited an enhanced amoxicillin and 5-fluorouracil release than the calcined samples. The composites demonstrated a strong antimicrobial activity against E. coli, S. aureus and S. epidermidis. The ST120 showed prolonged drug (AMX and 5-Fcil) release and antimicrobial efficacy than ST150 and calcined samples. This technique would be simple and rapid for composites preparation, to produce high quality crystalline, resorbable, mesoporous and bioactive nanocomposite (CHAp/agarose) powders. This work provides new insight into the role of agarose coated on bioceramics by solvothermal technique and suggests that CHAp/agarose composites powders are promising materials for filling of void in bone and drug delivery applications.

In vitro Evaluation of Mesoporous Carbonated Hydroxyapatite in MC3T3-E1 Osteoblast Cells

Nanoporous bioceramic recently has gained attention as a drug storage and release host in the therapeutic application. Mesoporous carbonated hydroxyapatite (MCHA) is a nanoporous bioceramic with pore sized ranged between 2-50nm. In order to use in drug delivery application, this material should demonstrate acceptable cytotoxic activity and osteoinductive response. Therefore, this study aimed to evaluate the effect of mesoporous carbonated hydroxyapatite on viability and alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts cell line. These parameters represent cytotoxicity level and osteinductivity capability of the materials. MC3T3-E1 cells were cultured in 25mg/ml extraction of mesoporous carbonated hydroxyapatite (meso-CHA) and non-porous CHA (np-CHA) for up to 7 days for viability and 14 days for ALP test. Results indicate that meso-CHA shows better cytotoxicity properties compare to np-CHA. Intracellular ALP of cells treated with meso-CHA was higher than np-CHA.

Pore Characteristics of Mesoporous Carbonated Hydroxyapatite Synthesised with Different Nonionic Surfactant and Carbonate Concentration

Mesoporous carbonated hydroxypatite (CHA) is a promising drug delivery agent for disease treatment and could be a carrier for different types of drugs and antibiotics. It is still a challenge to introduce pores to carry drugs within the mesoporous CHA and obtain high surface area nanoparticles. This study investigates the effect of different types of nonionic surfactant and carbonate concentration on the pore characteristic of mesoporous CHA. Mesoporous CHA is synthesised through the coprecipitation technique using nonionic surfactants as pore templates i.e., P123 and F127 with different carbonate concentration. The axial view of transmission electron microscopy (TEM) images shows the pores formed within the particles are distributed randomly, while the parallel view demonstrates that nanopore channels are developed within the CHA particles. Nitrogen adsorption analysis provides the surface area and Pore Size Distribution (PSD) of the nanoparticles. The PSD shows that CHA synthesis with P123 and F127 has similar pore size, around 28.9 nm, but different surface area. The results confirm the different types of surfactant templates has a positive effect on the pore characteristic, while carbonate precursor concentration does not significantly change surface area and pore size.

Emulsion fabrication of magnetic mesoporous carbonated hydroxyapatite microspheres for treatment of bone infection

Hydroxyapatite is widely used for bone filling materials because of its compositional similarities to bone mineral and excellent biocompatibility, but it does not possess good osteoinductivity and bactericidal properties. Herein, magnetic mesoporous carbonated hydroxyapatite microspheres (MEHMs) have been fabricated using CaCO3/Fe3O4 microspheres as sacrificial templates. The cetyltrimethylammonium bromide/Na2HPO4 solution/cyclohexane/n-butanol emulsion system serves as a microreactor, in which the CaCO3/Fe3O4 microspheres are converted to MEHMs via a dissolution–precipitation reaction. MEHMs with low crystallinity exhibit the hierarchical nanostructures constructed by nanoplates as building blocks with mesopores and macropores, which give them high drug loading–release properties. The controlled release of gentamicin significantly minimizes bacterial adhesion and prevents biofilm formation against S. epidermidis. The Fe3O4 nanoparticles are dispersed within the microspheres, which makes the MEHMs magnetic. The biocompatibility and osteoinductivity of the MEHMs have been investigated using human bone marrow stromal cells (hBMSCs) as cell models. The Fe3O4 nanoparticles in the MEHMs not only stimulate cell adhesion and proliferation, but also promote the osteogenic differentiation of hBMSCs. The excellent biocompatibility, osteoinductivity, drug loading–release properties and bactericidal properties give the MEHMs great potential as bone filling materials to treat bone infection.

Hydrothermal fabrication of magnetic mesoporous carbonated hydroxyapatite microspheres: biocompatibility, osteoinductivity, drug delivery property and bactericidal property.

Implant-associated infection is a serious problem in orthopaedic surgery. Ideal bone filling materials should not only possess excellent biocompatibility, but also have good anti-infection property and osteoinductivity. Herein, magnetic mesoporous carbonated hydroxyapatite microspheres (MHMs) have been fabricated according to the following stages: (i) preparation of CaCO3/Fe3O4 microspheres; and (ii) hydrothermal transformation of magnetic calcium carbonate microspheres into MHMs. MHMs possess well-defined 3D nanostructures constructed by nanoplates as building blocks. The mesopores and macropores exist in and among the nanoplates, respectively. The porous structure makes the MHMs possess a great drug loading efficiency of 73-82%. Gentamicin-loaded MHMs display a sustained drug release property, and the controlled release of gentamicin can prevent biofilm formation against S. epidermidis. Moreover, the MHMs possess a magnetic property with a saturation magnetization strength of 3.98 emu g-1 because Fe3O4 nanoparticles are dispersed in the microspheres. The in vitro cell tests indicate that the magnetic nanoparticles in the MHMs not only promote the cell adhesion and proliferation of human bone marrow stromal cells (hBMSCs), but also stimulate the osteogenic differentiation. MHMs exhibit excellent biocompatibility, osteoinductivity, drug delivery property and bactericidal property, so they have great application potential for the treatment of complicated bone defects.

The Effect of Surfactant Extraction Method on Pore Characteristics of Mesoporous Carbonated Hydroxyapatite

Incorporated with pore sizes of 2-50 nm, CHA was found to be a promising drug delivery agent for disease treatment and could be a carrier for different types of proteins. A desired drug delivery system should consist of an ordered pore network, optimum pore size, and volume, as well as a high surface area, to allow a high drug adsorption rate, controllable drug loading, and release. However, until now, most results are still not up to expectation; since the BET surface area and pore volume obtained has been rather low, compared to the existing mesoporous silica. The objective of this work was to investigate the effect of surfactant washing on the pore characteristics and the importance of this step in the synthesis process of mesoporous carbonated hydroxyapatite (CHA). In this study, mesostructured CHA particles were prepared, via a self-assembly mechanism, between CHA and non-ionic surfactant (P123), using the co-precipitation synthesis method. The synthesized mesoporous CHA samples were washed five times using different types of solvents for surfactant removal. A sphere-like particle shape of CHA was observed under SEM for all samples; regardless of the type of solvent used. The formation of CHA was confirmed by FTIR analysis, where the carbonate ion peaks were observed in the spectrums. It was found that the mesoporous CHA with a high surface area was synthesized when high polarity solvents were used during surfactant washing. These results imply that high surface area mesoporous CHA can be obtained through surfactant washing, without applying calcination for surfactant removal, which may change the structure of the CHA during heat treatment.

Bactericidal property and biocompatibility of gentamicin-loaded mesoporous carbonated hydroxyapatite microspheres

Implant-associated infection is a serious problem in orthopaedic surgery. One of the most effective ways is to introduce a controlled antibiotics delivery system into the bone filling materials, achieving sustained release of antibiotics in the local sites of bone defects. In the present work, mesoporous carbonated hydroxyapatite microspheres (MCHMs) loaded with gentamicin have been fabricated according to the following stages: (i) the preparation of the MCHMs by hydrothermal method using calcium carbonate microspheres as sacrificial templates, and (ii) loading gentamicin into the MCHMs. The MCHMs exhibit the 3D hierarchical nanostructures constructed by nanoplates as building blocks with mesopores and macropores, which make them have the higher drug loading efficiency of 70–75% than the conventional hydroxyapatite particles (HAPs) of 20–25%. The gentamicin-loaded MCHMs display the sustained drug release property, and the controlled release of gentamicin can minimize significantly bacterial adhesion and prevent biofilm formation against S. epidermidis. The biocompatibility tests by using human bone marrow stromal cells (hBMSCs) as cell models indicate that the gentamicin-loaded MCHMs have as excellent biocompatibility as the HAPs, and the dose of the released gentamicin from the MCHMs has no toxic effects on the hBMSCs. Hence, the gentamicin-loaded MCHMs can be served as a simple, non-toxic and controlled drug delivery system to treat bone infections.

Synthesis of Nanoporous Carbonated Hydroxyapatite Using Non-Ionic Pluronics Surfactant

Hydroxyapatite (HA) is a bioceramics that commonly used as bone substitute materials, coating materials and scaffolds in orthopedics. It is well known for its remarkable biocompatibility with natural human tissue. However, synthetic HA is different from biological apatite whereby apatites contain carbonate ion which is about 3-8wt% of the hard tissues of human body which described as carbonated hydroxyapatite (CHA). Hence, synthetic CHA may have a better bioactivity than HA and more widely used as biomaterials. This study described the synthesis and characterization of nanoporous carbonated hydroxyapatite (CHA) by co-precipitation method through self-organization mechanism with different type of non-ionic surfactants (P123 and F127). Diammonium hydrogen phosphate, (NH4)2HPO4 and calcium nitrate tetrahydrate, Ca (NO3)2.4H2O were used as starting materials for preparing the precursor for CHA powder. The ammonium carbonate, NH4HCO3 was used as the main source for carbonate ion. Synthesized powder was characterized using XRD, FESEM, EDS and FTIR. From the XRD result, pure HA phase was obtained for all samples. FTIR analysis results obviously showed the substitution of carbonate ion into the apatite and confirm the formation of CHA. The FTIR results also demonstrated that the surfactants had been removed completely through calcination process. SEM image revealed a sphere-like particle shape of CHA was produced after the calcinations. The mesoporous CHA with pore size 2-12 nm (F127) and 2-8 nm (P123) was synthesized.

Hierarchically nanostructured mesoporous carbonated hydroxyapatite microspheres for drug delivery systems with high drug-loading capacity

Hierarchically nanostructured mesoporous carbonated hydroxyapatite microspheres have a great potential for bone-implantable drug-delivery applications due to their large specific surface area, high drug-loading capacity (DLC), good biodegradability and bioactivity. However, monodisperse microspheres have rarely been reported due to the crystal orientation of carbonated hydroxyapatite. Herein, two synthesis strategies including an emulsion method and a hydrothermal method have been developed by using calcium carbonate microspheres as sacrificial templates, and the products are denoted EHMs and HHMs, respectively. Excitingly, the highest DLC of the EHMs (1.95 g vancomycin is loaded per gram of carrier) has been achieved among the reported porous hydroxyapatite so far. As compared with the EHMs, the HHMs have the lower DLC due to the smaller specific surface area and greater crystallinity. The in vitro drug release tests carried out by soaking drug-loaded carriers in simulated body fluid (SBF) reveal that the two drug delivery systems show a slow and sustained release of vancomycin and have the similar drug release trends. During the drug release, the EHMs and HHMs are degraded and converted to the bone-like apatite, which indicate that the two drug carriers have good in vitro bioactivity. In vitro cell experiments demonstrate that the two drug carriers have excellent biocompatibility, which can promote the adhesion and spreading of human bone marrow stromal cells (hBMSCs). Therefore, the two drug carriers, especially the EHMs, are promising for bone-implantable drug-delivery applications.

Hydrothermal fabrication of mesoporous carbonated hydroxyapatite microspheres for a drug delivery system

Mesoporous carbonated hydroxyapatite microspheres (MCHMs) with a particle size of ∼5μm have been fabricated hydrothermally by soaking calcium carbonate microspheres (CCMs) in a disodium hydrogen phosphate solution at 140°C. The transformation mechanism is a dissolution–precipitation reaction. After soaking in the disodium hydrogen phosphate solution, the calcium ions released from the CCMs react with phosphate ions in the solution to form carbonated hydroxyapatite nanoparticles. These nanoparticles aggregate to form mesopores with the pore size of 4.0–14.0nm. The MCHMs have been tested as vancomycin delivery systems due to the presence of the OH units in the carbonated hydroxyapatite structure, which provide these carriers of great affinity towards host drug molecules. In addition, in vitro tests into a simulated body fluid (SBF) demonstrate that the MCHMs are bioactive, since an apatite layer deposits on their surfaces after 3days of assay. Such MCHMs could be useful in developing new biomaterials and have potential use in implanting and drug delivery for tissue regeneration.

Fabrication of mesoporous carbonated hydroxyapatite microspheres by hydrothermal method

Mesoporous carbonated hydroxyapatite microspheres (MCHMs) have been converted from calcium carbonate microspheres (CCMs) by hydrothermal method. After soaking the CCMs in disodium hydrogen phosphate solutions, carbonated hydroxyapatite nanoparticles are formed via a dissolution–precipitation reaction. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) reveal that the as-obtained samples are calcium deficient hydroxyapatite with B-type CO 3 2− substitution. The transmission electron microscopy (TEM) indicates that the MCHMs are composed of many nanoparticles within the whole microspheres. These nanoparticles aggregate to form mesopores with a pore size of 4.5–14.0 nm among them. The formation mechanism of MHAMs has been discussed.

Magnetic mesoporous carbonated hydroxyapatite microspheres with hierarchical nanostructure for drug delivery systems

Magnetic mesoporous carbonated hydroxyapatite microspheres have been fabricated hydrothermally by using CaCO(3)/Fe(3)O(4) microspheres as sacrificial templates. The high drug-loading capacity and sustained drug release property suggest that the multifunctional microspheres have great potentials for bone-implantable drug-delivery applications.