Chemical structure of methylmethacrylate-2-[2′,3′,5′-triiodobenzoyl]oxoethyl methacrylate copolymer, radio-opacity, in vitro and in vivo biocompatibility

The properties of copolymers (physical, chemical, biocompatibility, etc.) depend on their chemical structure and microstructural characteristics. We have prepared radio-opaque polymers based on the copolymers of methyl methacrylate (MMA) and 2-[2′,3′,5′-triiodobenzoyl]oxoethyl methacrylate (TIBOM). The copolymerization reaction between TIBOM and MMA showed that the reactivity ratios were r1 = 0.00029 and r2 = 1.2146. The composition diagram is typical for a practically non-homopolymerizable monomer (TIBOM) and a very reactive monomer (MMA). The copolymers were analyzed on an X-ray microcomputed tomograph and they proved to be radio-opaque even at low concentrations of TIBOM. The biocompatibility was tested both in vitro (with J774.2 macrophage and SaOS-2 osteoblast like cells) and in vivo in the rat. These materials were found to be non-toxic and were well tolerated by the organism. These combined results led to the suggestion that this type of polymer could be used as dental or bone cements in place of barium or zirconium particles, which are usually added to provide X-ray opacity

Microct and preparation of β-TCP granular material by polyurethane foam method

Commercial ß-tricalcium phosphate (ß-TCP) is commercialy available in granules manufactured by sintering of powders. We have evaluated the different steps of the manufacturing process of ß-TCP ceramics granules prepared from blocks obtained with the polyurethane foam technology. Three types of slurry were prepared with 10, 15 and 25 g of ß-TCP per gram of polyurethane foam. Analysis was done by scanning electron microscopy, EDX, Raman spectroscopy and microcomputed tomography combined with image analysis. A special algorithm was used to identify the internal microporosity (created by the calcination of the foam) from the internal macroporosity due to the spatial repartition of the material. The low ß-TCP dosages readily infiltrated the foam and the slurry was deposited along the polymer rods. On the contrary, the highest concentration produced inhomogeneous infiltrated blocks and foam cavities appeared completely filled in some areas. 2D microcomputed sections and reconstructed 3D models evidenced this phenomenon and the frequency distribution of the thickness and separation of material trabeculae confirmed the heterogeneity of the distribution. When crushed, blocks prepared with the 25 g slurry provided the largest and irregular granulates

Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

PURPOSE: To understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease. METHODS: We identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons. RESULTS: The patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis. CONCLUSION: Mitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease

Three-Dimensional Characterization of the Vascular Bed in Bone Metastasis of the Rat by Microcomputed Tomography (MicroCT)

BackgroundAngiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography). They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. Methodology/Principal Findings We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer) was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts) were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels) was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. Conclusion This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular bed can be identified by a double reconstruction and allowed a quantitative evaluation of angiogenesis upon time

Cobalt, chromium and nickel affect hydroxyapatite crystal growth in vitro

Metals are widely used in orthopaedics and recent studies have reported that patients with metal implants have a significant increase of metal levels in serum and synovial fluid. Femoral neck fracture occurred in some patients with metal-on-metal implants for unknown reasons. Recently, bone quality has emerged as an important factor of bone strength and few studies have investigated the effects of metal ions on hydroxyapatite properties. In the present study, we investigated the effects of Co²⁺, Cr³⁺ and Ni²⁺ on hydroxyapatite (HA) growth in vitro, using carboxymethylated poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial for calcification. We have demonstrated that metal ions reduced the quantity of mineral formed at the surface of the polymer and decreased the ratio Ca/P by 1.12-, 1.05- and 1.08-fold for Cr²⁺, Cr³⁺ and Ni²⁺ respectively. Furthermore, the size of calcospherites was significantly increased in the metal-doped HA compared to the controls, indicating a possible effect of metal ions on the crystal lattice. Indeed, the presence of metal ions increased the crystal size as well as the crystallinity of HA and reduce the lattice parameter c of the HA framework. The information obtained from this work suggests that the quality of the mineral around metallic implants could be altered. However, further investigation should be conducted to further elucidate the effects of metal incorporation on bone mineral and the functional consequences