Cytotoxicity Study of UV-Laser-Irradiated PLLA Surfaces Subjected to Bio-Ceramisation: A New Way towards Implant Surface Modification.

In this research we subjected samples of poly(L-lactide) (PLLA) extruded film to ultraviolet (193 nm ArF excimer laser) radiation below the ablation threshold. The modified film was immersed in Simulated Body Fluid (SBF) at 37 °C for 1 day or 7 days to obtain a layer of apatite ceramic (CaP) coating on the modified PLLA surface. The samples were characterized by means of optical profilometry, which indicated an increase in average roughness (Ra) from 25 nm for the unmodified PLLA to over 580 nm for irradiated PLLA incubated in SBF for 1 day. At the same time, the water contact angle decreased from 78° for neat PLLA to 35° for irradiated PLLA incubated in SBF, which suggests its higher hydrophilicity. The obtained materials were investigated by means of cell response fibroblasts (3T3) and macrophage-like cells (RAW 264.7). Properties of the obtained composites were compared to the unmodified PLLA film as well as to the UV-laser irradiated PLLA. The activation of the PLLA surface by laser irradiation led to a distinct increase in cytotoxicity, while the treatment with SBF and the deposition of apatite ceramic had only a limited preventive effect on this harmful impact and depended on the cell type. Fibroblasts were found to have good tolerance for the irradiated and ceramic-covered PLLA, but macrophages seem to interact with the substrate leading to the release of cytotoxic products.

Innovative delivery of siRNA to solid tumors by super carbonate apatite.

RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.

[Neoplasm mortality in population residing near extracting and processing apatite ore facilities]. / Smertnost' ot zlokachestvennykh novoobrazovanii naseleniia, prozhivaiushchego vblizi predpriiatiia po dobyche i pererabotke apatitovykh rud.

Increased mortality with malignancies in population who reside near enterprises processing Kolsky apatite-nepheline ores is determined mostly by mortality among an "occupational group" engaged into this production.

Resorbable calcium phosphate bone substitute.

The in vitro and in vivo properties of a novel, fully resorbable, apatitic calcium phosphate bone substitute (ABS) are described. The ABS was prepared from calcium phosphate precursors that were hydrated to form an injectable paste that hardens endothermically at 37 degrees C to form a poorly crystalline apatitic calcium phosphate (PCA). The PCA reaction product is stable in vivo as determined by FTIR and XRD analysis of rabbit intramuscular implants of ABS retrieved 4, 7, and 14 days postimplantation. Bone formation and resorption characteristics of the ABS material were characterized in a canine femoral slot defect model. Femoral slot defects in dogs were filled with either autologous bone implants or the ABS material. Sections of femoral bone defect site from animals sacrificed at 3, 4, 12, 26, and 52 weeks demonstrated that new bone formation proceeded similarly in both autograft and ABS filled slots. Defects receiving either material were filled with trabecular bone in the first 3 to 4 weeks after implantation; lamellar or cortical bone formation was well established by week 12. New bone formation in ABS filled defects followed a time course comparable to autologous bone graft filled defects. Histomorphometric evaluation of ABS resorption and new bone formation indicated that the ABS material was greater than 99% resorbed within 26 weeks; residual ABS occupied 0.36+/-0.36% (SEM, n = 4) of the original defect area at 26 weeks. Quantitatively and qualitatively, the autograft and ABS were associated with similar new bone growth and defect filling characteristics.

[Clinical application of AW glass ceramic prosthesis in spinal surgery].

Bone prosthesis of apatite- and wollastonite-containing glass-ceramic (AW-GC), a new synthesized material, is known to be excellent in bonding directly with adjacent living bone tissue, in having strong mechanical strength and no toxic effects, in experimental studies. In spinal surgery, massive and strong bone grafts are required for reconstruction of the spinal column affected by a tumor, trauma, or a degenerative disease. However, utilization of bone allograft is not yet socially accepted in Japan and also there are other barriers against the supply of allograft bone. In the present study, AW-GC bone prosthesis was used for reconstructive surgery for various spinal diseases and follow-up studies were performed for an average of 14.9 months (range: 2-36 mo). The clinical results were satisfactory. Thirty patients (males: 17 and females: 13) with an age range of 40-75 years (mean: 55.3 years) were reviewed in this study. Preoperative diagnoses for which an AW-GC prosthesis was required were as follows; vertebral prosthesis: 15 with metastatic tumor of the spine, 3 with burst fracture of the thoraco-lumbar spine; vertebral spacer: 6 with degenerative spondylolisthesis, 2 with isthmic spondylolisthesis, 2 with lumbar intervertebral disc herniation, and one with spinal canal stenosis. Patient's satisfaction, roentgenographic evaluation, laboratory data on blood and urine, and toxic effects were examined in these patients. As a result, the patient's satisfaction for the AW-GC bone prosthesis was high, and the initial fixation and long term stability were excellent. For kyphotic deformity and scoliosis, postoperative correction could be maintained in two patients where correction was attempted, and the usefulness of AW-GC prosthesis as a spinal prosthesis was confirmed. Good bone formation around the prosthesis was observed with time. The clear zone (radiolucent line between ceramic and bone) tended to decrease or disappear. There were no systemic or local toxic side-effects considered to be due to the AW-GC bone prosthesis, or no abnormalities in the laboratory data. These findings suggested that the AW-GC bone prosthesis is a new biomaterial with excellent properties which can be successfully substituted for bone graft in reconstructive spinal surgery.

Assessment of the nasal mucosa in workers exposed to the prolonged effect of phosphorite and apatite dusts.

One hundred and thirty one workers occupationally exposed to phosphorite and apatite dusts and a control group underwent repeated laryngological and cytological examinations of nasal mucosa smears. The clinical examination showed chronic simple or atrophic rhinitis. The cytological test revealed metaplasia of the respiratory epithelium towards squamous epithelium in all smears. Both the rate of catarrhal changes and the degree of epithelial metaplasia varied with the duration of exposure.

Comparison of the acute inflammation induced by calcium pyrophosphate dihydrate, apatite and mixed crystals in the rat air pouch model of a synovial space.

Pure monoclinic or triclinic calcium pyrophosphate dihydrate (CPPD) crystals, apatite crystals or mixtures of these crystals were injected into the synovial-like space created by the rat air pouch to compare the acute inflammation induced by these crystals. Fluids were withdrawn 6 h after injection and examined for leukocyte counts, protease, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels. CPPD crystals (especially monoclinic CPPD) induced higher numbers of leukocytes, and more protease, PGE2 and TNF than apatite. CPPD seemed to play a predominant role in the acute inflammation induced by mixed crystals.

SEM-EPMA observation of three types of apatite-containing glass-ceramics implanted in bone: the variance of a Ca-P-rich layer.

The progressive changes of a Ca-P-rich layer between bone and three types of apatite-containing glass-ceramics of the same chemical composition: MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF2 0.5 (in weight ratio) were examined. Plates (15 mm X 10 mm X 2 mm, mirror surface) containing apatite (35 wt%) (designated A-GC), apatite (35 wt%) and wollastonite (40 wt%) (designated A.W-GC), and apatite (20 wt%), wollastonite (55 wt%), and whitlockite (15 wt%) (designated A.W.CP-GC) were prepared. They were implanted into the tibia of mature male rabbits for 5 days, 10 days, 20 days, 30 days, 60 days, 6 months, and 12 months. All three types of glass-ceramics showed direct bonding to the bone 30 days after implantation. It was observed by SEM-EPMA 30 days after implantation that Si and Mg content decreased, P content increased, and Ca content did not change across the reactive zone from the glass-ceramics to bone. The level of P and Si in the A.W.CP-GC changed five days after implantation. In A.W-GC and A-GC, a little change in P and Si levels was observed between 10 and 20 days after implantation. The width of reactive zone was narrowest with A-GC, wider with A.W-GC, and widest with A.W.CP-GC. The dissolution of glass-ceramics stopped 6 months after implantation. This phenomenon shows that the glass-ceramics may be suitable for clinical use.

[Experimental silicosis. Evaluation of the silicogenic properties of apatites and phosphorites]. / Doswiadczalna pylica krzemowa. Ocena pylicotwórczych wlasciwosci apatytów i fosforytów.

White rats were intratracheally injected with 50 mg of apatite or phosphorite dust. The animals were killed 3, 6 and 10 months after the injection. Fibrogenic properties were evaluated on the basis of biochemical and histopathological studies. It was found that the dusts under examination after 3 months of experiment induced a statistically significant increase of wet and dry lungs weight, of hydroxyproline and lipids content in the lungs, and intrathroacic lymph nodes as compared with the control group. After 3 and 10 months, a further but statistically insignificant increase of hydroxyproline content in lungs and of wet lung weight was observed, as compared with animals in the 3--months experiment. The obtained values of fibrogenic action indices for apatite and phosphorite dusts were quite similar to the values obtained in animals injected with inert dust of titanium dioxide. They were 4--5 times lower than the indices obtained after administrating the river sand--a dust of strong fibrogenic properties. Histopathological studies primarily revealed inflammatory changes in bronchial and peribronchial tissue, and focal emphysematous changes, whereas no features of a progressive development of fibrous changes in lungs. The MAC values of 6 mg/m3 for phosphorite dust of 8 mg/m3 for apatite dust--were suggested.

Arthritis associated with apatite crystals.

Needle-shaped crystals of 75 to 250 A diameter have been identified by transmission electron microscopy in clumps within synovial fluid mononuclear cell vacuoles in a variety of joint diseases. These crystals, similar to those previously associated with calcific periarthritis, were seen in acute undiagnosed arthritis and in exacerbations of osteoarthritis where they may be inducing a synovitis similar to that seen with urate and pyrophosphate crystals in gout and pseudogout. By light microscopy purple staining cytoplasmic inclusions or extracellular globules can suggest the presence of clumps of these crystals. Apatite clumps can also occasionally appear as small birefringent chunks or rods and thus might mimic urate or calcium pyrophosphate. Ultrastructural appearance, electron probe analysis, and X-ray diffraction pattern were those of apatite. Experimental injection of hydroxyapatite crystals into dog knee joints produces inflammation supporting the potential role for these crystals in joint disease.