Tomohiro Umeda

Effects of blood on bone cement made of calcium phosphate: Problems and advantages

In recent years, calcium phosphate cements (CPCs) have frequently been used as bone substitutes in the field of orthopedic surgery. When CPC is used as a bone substitute in vivo, blood contamination is unavoidable. To date, however, no detailed study has been conducted focusing on how the physical properties of CPCs would change under the influence of blood. In this study, the effects of blood contamination on Biopex-R (BPR, PENTAX, Tokyo) are examined in vitro and in vivo. The compressive strength of BPR after setting decreased depending on the amount of contaminating blood. The BPR, which has set in vivo, not only has a fragile surface due to the contamination by blood, but also has a propensity to shorten and be destroyed during the early postoperative stage, especially in the bone exposed to loads. On the other hand, radiographic and histological features in vivo indicated that the absorption and the bone replacement of BPR were stimulated by blood contamination. In the clinical evaluation, the patients own peripheral venous blood was added to the BPR. One year after the surgery, the absorption was noted around the hardened BPR. To advance CPCs (including BPR) as bioabsorbable bone replaceable materials, it is essential to utilize the patients own blood in combination with the CPC.

Morphological and microstructural changes during the heating of spherical calcium orthophosphate agglomerates prepared by spray pyrolysis

The microstructural changes taking place during heating of calcium orthophosphate (Ca3(PO4)2) agglomerates were examined in this study. The starting powder was prepared by the spray-pyrolysis of calcium phosphate (Ca/P ratio=1.50) solution containing 1.8 mol·L−1 Ca(NO3)2, 1.2 mol·L−1 (NH4)2HPO4 and concentrated HNO3 at 600 °C, using an air-liquid nozzle. The spray-pyrolyzed powder was found to be composed of dense spherical agglomerates with a mean diameter of 1.3 μm. This powder was further heat-treated at a temperature between 800 and 1400 °C for 10 min. When the spray-pyrolyzed powder was heated up to 900 °C, only β-Ca3(PO4)2 was detected, and the mean pore size of the spherical agglomerates increased via the (i) elimination of residual water and nitrates, (ii) rearrangement of primary particles within the agglomerates, (iii) coalescence of small pores (below 0.1 μm), and (iv) coalescence of agglomerates with diameters below 1 μm into the larger agglomerates. Among the heat-treated powders, pore sizes within the spherical agglomerates were observed to be the largest (mean diameter: 1.8 μm) for the powder heat-treated at 900 °C for 10 min. With an increase in heat-treatment temperature up to 1000 °C, the spherical agglomerates were composed of dense shells. Upon further heating up to 1400 °C, the hollow spherical agglomerates collapsed as a result of sintering via the phase transformation from β- to α-Ca3(PO4)2 (1150 °C), thus leading to the formation of a three-dimensional porous network.

Fabrication of Novel Hemostatic Film with Oxidized Cellulose and Sugar-Containing Hydroxyapatite

The novel hemostatic film for the surgery of bone diseases was fabricated using TEMPO(2,2,6,6-tetramethylpiperidine-1-oxyl)-oxidized cellulose nanofibers (TOCNs), and phosphoryl oligosaccharides of calcium (POs-Ca) or sugar-containing hydroxyapatite (s-Ca10(PO4)6(OH)2; s-HAp). Three kinds of the hydrophilic and transparent films with the thicknesses of 10 to 20 μm were fabricated, i.e., TOCN, POs-Ca-added TOCN and s-HAp-added TOCN films. Among these films, the uptake amount of the simulated body fluid by s-HAp-added TOCN film was as high as 5,543%, which was expected to quickly stop bleeding of larger amount of blood for the hemostasis.

Properties of novel bone hemostat prepared using sugar-modified hydroxyapatite, phosphoryl oligosaccharides of calcium and thermoplastic resin

A novel hemostatic agent was prepared using phosphoryl oligosaccharides of calcium (POs-Ca), hydroxyapatite (Ca10(PO4)6(OH)2; HAp) obtained by the hydrolysis of POs-Ca or sugar-containing HAp (s-HAp; 60.3 mass% calcium-deficient HAp and 39.5 mass% organic materials, Ca/P ratio = 1.56) and thermoplastic resin (the mixture of random copolymer of ethylene oxide/propylene oxide (EPO) and polyethylene oxide (EO); EPO : EO : water = 25 : 15 : 60 (mass ratio); 25EPO-15EO). The gel formed by mixing 25EPO-15EO with water (25EPO-15EO/water mass ratio: 0.20) was flash frozen at -80°C, freeze-dried at -50°C for 15 h and then ground using mixer. The consistency conditions of hemostats mixed with POs-Ca or s-HAp were optimized for the practical uses. The mean stanching times of hemostats were: s-HAp/25EPO-15EO (8.2 h; s-HAp/25EPO-15EO = 0.20) > 25EPO-15EO (5.3 h) > POs-Ca/25EPO-15EO (4.7 h; POs-Ca/25EPO-15EO = 0.20). The gentamicin, a typical antibiotic agent, loaded s-HAp/25EPO-15EO composite hemostat showed the steady state releasing in phosphate buffered saline till 10 h immersion at 37.0°C.

Fabrication of Novel Film Containing Hydroxyapatite Nanoparticles/Cellulose Derivative and its Evaluation

The novel and flexible film for biomedical application could be fabricated by using hydroxyapatite (Ca10(PO4)6(OH)2; HAp) and cellulose derivatives. Firstly, 0.2 mass% 2,2,6,6-tetramethylpitiperidine-1-oxyl radical (TEMPO) oxidized cellulose (TOC) was agitated at 20,000 rpm for 3 min and then ultrasonically treated for 20 min at the frequency of 45,000 Hz to form the solution containing TOC nanofiber (TOCN). After the nano-sized HAp powder was put into TOCN solution (100 cm3; HAp/TOCN mass ratio of 0.10 or 0.50), the composite film was fabricated by drying it at 50°C for 3 d. The TOCN film with no HAp addition (the thickness: approximately 15 μm) possessed transparency, flexibility and high tensile strength (mean strength: 193 MPa). On the other hand, the tensile strength of HAp-TOCN composite film (thickness: 30 μm) was reduced from 60.1 to 50.2MPa with increasing HAp/TOCN mass ratio from 0.10 to 0.50. When the HAp/TOCN composite films were immersed in SBF at 37.0°C for 2 weeks, the spherical apatite particles were notably found to form on their surfaces.

Fabrication of Flexible Porous Calcium-Deficient Apatite -Alginate Composite and Its Evaluation

The calcium-deficient apatite (Ca9.36(HPO4)0.74(PO4)5.26(OH)1.26nH2O (Ca/P ratio=1.56): DAp) – alginate (AG) composite was fabricated by the ice crystal sublimation technique. The starting whisker-like calcium-deficient apatite (w-DAp) powder with long-axis length of 62.6 μm and short-axis length of 2.85 μm was prepared by the homogeneous precipitation technique. After mixing the w-DAp with AG paste (DAp/AG ratio: 10), the mixture was flash frozen at a temperature between −5 and −196°C. The frozen materials were further lyophilized at -50°C for 24 h under reduced pressure and put into 1 mol-dm−3 CaCl2 solution at room temperature for 24 h The microscopic observation showed that the pore size of w-DAp-AG composite increased from ~20 to ~100 μm with decreasing concentration of starting AG paste from 7.5 to 2.5 mass% and with decreasing freezing temperature from −196°C down to −5°C. The maximum porosity of w-DAp-AG composite, which was fabricated using 2.5 mass% AG at the freezing temperature of -5°C, attained 92.3%.

Properties of Calcium Phosphate Powder Prepared from Phosphoryl Oligosaccharides of Calcium

The phosphoryl oligosaccharides of calcium (POC), extracted from potato starch, are composed of phosphorus oligosaccharides and calcium ions. Ultrafine calcium phosphate particles, whose main phase was hydroxyapatite (Ca10(PO4)6(OH)2: HAp), could be prepared through the hydrothermal treatment of POC solution at a temperature between 110 and 130°C; X-ray diffraction indicated the crystallinity of HAp in the resulting powder to be poor and similar to that of living bone. The present HAp powder was regarded to be calcium deficient carbonate apatite with the OH- group being partly substituted by a carbonate (CO3 2-) group. The solubility of the resulting powder in dilute hydrochloric acid was higher compared to that of commercially available HAp, suggesting excellent bioabsorbability for the present powder.

Preparation of Hollow and Spherical β-Calcium Orthophosphate Agglomerates: Effect of Organic Compound Addition to the Spraying Solution

Hollow and spherical β -calcium orthophosphate (β-Ca3(PO4)2: β -TCP) agglomerates were prepared by the spray-pyrolysis of solution containing 1.8 mol·dm -3 of Ca(NO3)2, 1.2 mol·dm -3 of (NH4)2HPO4, 0.1~0.4 mol·dm -3 of organic compounds (citric acid, L-maleic acid and glutaric acid) and concentrated HNO3 at 600°C, using an air-liquid nozzle. This spray-pyrolyzed β -TCP powder was further heat-treated at 900°C for 10 min in order to produce the porous agglomerates following burnout of residual carbon. Regardless of the different organic compound utilized (concentration in the starting solution: 0.2 mol·dm -3 ), most of the agglomerate diameters were in the range of 1 to 4 μm. The specific surface areas were arranged as follows: 10.5 m 2 ·g -1 (glutaric acid) > 8.4 m 2 ·g -1 (L-maleic acid) > 6.5 m 2 ·g -1 (citric acid) > 1.7 m 2 ·g -1 (no addition). Pore-size distributions for the three kinds of agglomerates indicated the majority of pore sizes to be approximately 1 μm. The dissolution of Ca and P ions from the β -TCP powder into physiological saline was faster compared to that of powders spray-pyrolyzed without the use of an organic compound, suggesting excellent bioresorbability for the present powders.