Spherical Hydroxyapatite Granules Research Articles

A Method to Prepare Hollow Spherical Hydroxyapatite Granules for Drug Delivery

Abstract A suitable microenvironment provided by artificial granule scaffold plays a critical regulatory role in bone repairing progression. Till now, it is still a challenge to prepare large hydroxyapatite granules (millimetre level) which provide beneficial physical and chemical stimulation for bone reconstruction. Herein, we developed a facile synthetic strategy for synthesizing hydroxyapatite granules by a repaid gelling method. Also, the satisfying drug-releasing behavior of these granules further proves their potential prospect for bone tissue engineering as bone filler.

Nanocrystalline spherical hydroxyapatite granules for bone repair: in vitro evaluation with osteoblast-like cells and osteoclasts

Conventionally sintered hydroxyapatite-based materials for bone repair show poor resorbability due to the loss of nanocrystallinity. The present study describes a method to establish nanocrystalline hydroxyapatite granules. The material was prepared by ionotropic gelation of an alginate sol containing hydroxyapatite (HA) powder. Subsequent thermal elimination of alginate at 650°C yielded non-sintered, but unexpectedly stable hydroxyapatite granules. By adding stearic acid as an organic filler to the alginate/HA suspension, the granules exhibited macropores after thermal treatment. A third type of material was achieved by additional coating of the granules with silica particles. Microstructure and specific surface area of the different materials were characterized in comparison to the already established granular calcium phosphate material Cerasorb M(®). Cytocompatibility and potential for bone regeneration of the materials was evaluated by in vitro examinations with osteosarcoma cells and osteoclasts. Osteoblast-like SaOS-2 cells proliferated on all examined materials and showed the typical increase of alkaline phosphatase (ALP) activity during cultivation. Expression of bone-related genes coding for ALP, osteonectin, osteopontin, osteocalcin and bone sialoprotein II on the materials was proven by RT-PCR. Human monocytes were seeded onto the different granules and osteoclastogenesis was examined by activity measurement of tartrate-specific acid phosphatase (TRAP). Gene expression analysis after 23days of cultivation revealed an increased expression of osteoclast-related genes TRAP, vitronectin receptor and cathepsin K, which was on the same level for all examined materials. These results indicate, that the nanocrystalline granular materials are of clinical interest, especially for bone regeneration.

Synthesis of spherical hydroxyapatite granules with interconnected pore channels using camphene emulsion

The aim of this study was to fabricate porous spherical hydroxyapatite (HA) granules with interconnected pore channels for use as a bone graft substitute. Various weights of camphene porogen were mixed with nano-sized HA powder (camphene/HA = 0, 10, 30, 50, 70, and 90% w/w) and 10% gelatin aqueous solution then added to the mixture. The water-in-oil emulsion method was employed to obtain spherical-shaped granules, of which those 1000-2000 μm in diameter were selectively classified using a standard sieve set. Thermogravimetric analysis and X-ray diffraction were used to determine optimal sintering conditions. The sintered granules were characterized using field emission-scanning electron microscopy (FE-SEM), microcomputed tomography, and porosimetry. The pore size and porosity of spherical HA granules increased with the addition of camphene. Granules with a HA/camphene ratio of 90% (HG90) demonstrated macropores (>50 μm) with interconnected pore channels (porosity: 58.49%). In addition, FE-SEM examination of HG90 coated with polycaprolactone showed that the granule may hold promise as a drug delivery carrier. We concluded that these HG90 granules merit consideration as a bone graft substitute or drug delivery carrier in bone tissue engineering.

Drug-loaded porous spherical hydroxyapatite granules for bone regeneration

Porous spherical hydroxyapatite (HAp) granules, which are not only can be used for bone void filler, but also drug delivery systems, were prepared using a liquid nitrogen method. Various pore and channel structures of spherical granules were obtained by adjusting the ratio of water to HAp powder and the amount of sodium chloride (NaCl). By using the water to powder ratio at 2.0ml/g and the amount of NaCl at 15wt% by powder, the spherical granules have optimal pore volume, micro-channel structure and strength to handle as well as the ability to work as a drug delivery system. When the NaCl content was 15wt%, the micro-channel structure was changed, but the pore volume was maintained. For the drug release test, dexamathasone (Dex) was loaded as a model drug on the prepared HAp granules by the immersion method, and the drug release behavior was curved by a UV/vis spectrophotometer. As a result, different drug release behavior was observed according to micro-channel structural differences. Therefore, it was concluded that the NACl could be applied as the pore and micro-channel structure control agent. Porous spherical HAp granules, which were fabricated by a liquid nitrogen method, show potential as bone void filler with the ability of controlled drug release.

Preparation of microstructured hydroxyapatite microspheres using oil in water emulsions

Hydroxyapatite (HAP) microspheres with peculiar spheres-in-sphere morphology were prepared by using oil-in-water emulsions and solvent evaporation technique. Ethylene vinyl acetate co-polymer (EVA) was used as the binder material. Preparation of HAP/EVA microspheres was followed by the thermal debinding and sintering at 1150°C for 3 h to obtain HAP microspheres. Each microsphere of 100–1000 μm was in turn composed of spherical hydroxyapatite granules of 2–15 (μm size which were obtained by spray drying the precipitated HAP. The parameters such as percentage of initial HAP loading, type of stabilizer, concentration of stabilizer, stirring speed and temperature of microsphere preparation were varied to study their effect on the particle size and geometry of the microspheres obtained. It was observed that these parameters do have an effect on the size and shape of the microspheres obtained, which in turn will affect the sintered HAP microstructure. Of the three stabilizers used viz. polyoxyethylene(20) sorbitan monopalmitate (Tween-40), sodium laurate and polyvinyl alcohol (PVA), only PVA with a concentration not less than 0.1 wt% showed controlled stabilization of HAP granules resulting in spherical microspheres of required size. Morphologically better spherical microspheres were obtained at 20°C. Increasing the stirring speed produced smaller microspheres. Smaller microspheres having size < 50 μm were obtained at a stirring speed of 1500 ±50 rpm. A gradual decrease in pore size was observed in the sintered microspheres with increase in HAP loading.

Method for Tailoring and Control the Morphology, Size and Porosity of Calcium Phosphate Granules

Hydroxyapatite (HA) is the calcium-phosphate material with composition closest to that of human bone, what makes it suitable for osseous implant purposes, namely as fillers, spacers and bone grafts substitutes. This study is aimed at the development of a method to produce porous spherical hydroxyapatite granules. The process involves the spraying of a suspension with different amounts of a setting agent to a setting media. The tailor and the control of the morphology, size and porosity of the granules were attained by adjusting the nozzle diameter, the pressure of air flow and the distance between the nozzle and the setting media.

A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release

This study is aimed at the development of a method to fabricate porous spherical hydroxyapatite (HA) granules, which can be impregnated with a drug. These drug-loaded particles can be used as a system for targeted and time-controlled drug delivery, e.g. in bone surgery. The method to produce porous granules is based on liquids immiscibility effect. A suspension of HA powder in aqueous solution of gelatin and oil as a dispersion media were used. By stirring the mixtures of these immiscible liquids, granules of 50–2000μm diameter can easily be produced. Dependence of the granules characteristics on the preparation route was studied. In vivo experiments were performed to simulate drug release kinetics from the granules to the blood of rats.

Development of porous spherical hydroxyapatite granules: application towards protein delivery.

A new method for the preparation of porous spherical hydroxyapatite granules is reported. It may be clinically applied towards orthopaedic or maxillofacial surgery as fillers or packing materials, and as biological chromatography supports. Its application towards delivery of macromolecules or protein drugs is discussed utilizing human serum albumin (HSA) as a model protein.