Mechanochemical synthesis of zinc-apatitic calcium phosphate and the controlled zinc release for bone tissue engineering

Abstract

In this study, in order to control zinc (Zn)-release from calcium phosphate (CaP), the crystalline forms of CaP-containing Zn were modified by wet ball milling and/or heat treatment. The CaP (CaO:CaHPO4:ZnO = 7:20:3, molar ratio) was ground in a ball mill with the addition of purified water, and the ground products were heated to 400 °C and 800 °C. The physicochemical properties of these ground products were measured by powder X-ray diffraction (XRD), infrared spectroscopy (IR), scanning electron microscopy and energy-dispersive X-ray spectroscopy. Zn release characteristics from the samples were evaluated using a dissolution tester. The results of XRD and IR suggested that the structures of the starting materials were destroyed after 2.5 h of grinding, and new apatite-like amorphous solid containing Zn was generated. The Zn-release from the ground products was markedly suppressed after 2.5 h of grinding.

Analytical Evaluation of Wet and Dry Mechanochemical Syntheses of Calcium-Deficient Hydroxyapatite Containing Zinc Using X-ray Diffractometry and Near-Infrared Spectroscopy

“…In wet grinding, the diffraction peaks of all raw materials significantly decrease with increasing grinding time. In the XRD pattern of the product obtained by grinding for more than 2 h, broad diffraction peaks at 26.0 and 32.0° ascribed to HAP are observed, as reported previously [ 54 ]. In contrast, in dry grinding, the diffraction peaks attributed to CHPD and CaO significantly decrease after approximately 1 h of grinding; however, the intensity of the original ZnO diffraction peak remains unchanged.…”

“…The in vitro dissolved amount of Zn in the sample powders was measured in phosphate-buffered saline (PBS; pH 6.2). The dissolution test was performed using the paddle method at 100 rpm in 200 mL of PBS at 37.0 ± 0.5 °C [ 54 ]: Each powder sample (20 mg) was examined using a dissolution tester (NTR-6100, Toyama Sangyo Co. Ltd., Osaka, Japan), and the sample solution (1 mL) was collected after 10 min. The Zn concentration was quantified using a commercially available Zn assay kit (5-Br-PAPS, Fuji Film Chemical Industry Co., Tokyo, Japan) with an ultraviolet–visible absorption spectrometer (UV/VIS; UV2550, Shimadzu Co., Kyoto, Japan) at 560 nm.…”

“…Studies on the mechanochemical synthesis of calcium phosphates by wet grinding have revealed that Ca 2+ replaces Sr 2+ in this process [ 51 , 52 , 53 ]. In the previous report [ 54 ], Zn-doped calcium phosphate (ZnAP) was prepared via a simple wet mechanochemical synthesis using centrifugal agate ball milling. Crystalline properties of ZnAP were sufficiently characterized by qualitative methods, such as powder X-ray analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy, the nitrogen gas adsorption and in vitro Zn release test, and the results clearly indicated that the formation of Ca-deficient HAP containing Zn during grinding [ 54 ].…”

“…In the previous report [ 54 ], Zn-doped calcium phosphate (ZnAP) was prepared via a simple wet mechanochemical synthesis using centrifugal agate ball milling. Crystalline properties of ZnAP were sufficiently characterized by qualitative methods, such as powder X-ray analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy, the nitrogen gas adsorption and in vitro Zn release test, and the results clearly indicated that the formation of Ca-deficient HAP containing Zn during grinding [ 54 ]. Biomedical activities of the ZnAP were optimal ranges for bone regeneration medicine by evaluating various pharmaceutical properties.…”

“…An obtained injectable suspension formulation using ZnAP can be applied to any parts of the body. At the injection site, the nanoparticles with bioaffinity are phagocytosed by cells such as macrophages, and the particles dissolved and release Zn [ 54 ], so, sustained Zn release rate could be freely controlled. The result indicated that the injectable ZnAP suspension formulation may be useful practical dosage form for the slow release of Zn.…”