Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.
We compared the composition and biological activity of fetal calf serum and platelet lysate from donor platelet concentrate. In platelet lysate, the concentrations of alkaline phosphatase, lactate dehydrogenase, creatinine, and mineral metabolism parameters were lower, while parameters of lipid and protein metabolism were higher than in fetal calf serum. The concentrations of growth factors (platelet-derived (AA, AB, BB), vascular endothelial, insulin-like, and transforming growth factor β) in platelet lysate 1.7-148.7-fold surpassed the corresponding parameters in fetal calf serum. After replacement of fetal calf serum with platelet lysate in the culture medium (0, 25, 50, 75, and 100%), the count of multipotent mesenchymal stromal cells on day 7 (in comparison with day 1) increased by 154.8, 206.6, 228.2, 367.7, and 396.5%, respectively. Thus, platelet lysate can be an adequate non-xenogenic alternative for fetal calf serum.
We analyzed the research data on antitumor effects of a wide range of ferrocene compounds and discussed possible mechanisms of their bioactivities. Current trends in the study of antican cer effects of ferrocene derivatives were considered. Promising ways in the design of low toxicity anticancer ferrocene based drugs of new generation were outlined. * Dedicated to the 60th anniversary of the A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (INEOS RAS). The review was written on the initiative and with the active participation of Yu. S. Nekrasov who served with good faith and fidelity for INEOS RAS for more than 40 years. † Deceased.
aThe toxicity of ferrocenylethyl benzotriazole (1) and other ferrocene compounds including ferrocenylmethyl benzimidazoles (4,5,6,11), ferricenium salts (3,9,10) and ferrocenylmethyl adenine (7), was studied. All ferrocene complexes under investigation showed low or medium toxicities. On the basis of an earlier model of chemical carcinogenesis, the antitumor activity of ferrocenylalkyl azoles 1, 8 and ferricenium salts 9, 10 was studied in vivo in the so-called sub-capsular test on human tumors. This effectiveness was compared with that of cisplatin. A series of ferrocenylalkyl azoles were synthesized by interacting azoles either with α-hydroxyalkyl ferrocenes FcC(OH)R 1 R 2 in organic solvent in the presence of aqueous HBF 4 in quantitative yields or with trimethyl(aminomethyl)ferrocene iodide in an aqueous-basic medium in good yields. The X-ray determinations of molecular and crystal structures of α-(1-benzotriazolyl)ethylferrocene (1) and α-(1-naphthatriazolyl)ethylferrocene (12) were performed.
Mesoporous hydroxyapatite (HA) and iron(III)-doped HA (Fe-HA) are attractive materials for biomedical, catalytic, and environmental applications. In the present study, the nanopowders of HA and Fe-HA with a specific surface area up to 194.5 m2/g were synthesized by a simple precipitation route using iron oxalate as a source of Fe3+ cations. The influence of Fe3+ amount on the phase composition, powders morphology, Brunauer–Emmett–Teller (BET) specific surface area (S), and pore size distribution were investigated, as well as electron paramagnetic resonance and Mössbauer spectroscopy analysis were performed. According to obtained data, the Fe3+ ions were incorporated in the HA lattice, and also amorphous Fe oxides were formed contributed to the gradual increase in the S and pore volume of the powders. The Density Functional Theory calculations supported these findings and revealed Fe3+ inclusion in the crystalline region with the hybridization among Fe-3d and O-2p orbitals and a partly covalent bond formation, whilst the inclusion of Fe oxides assumed crystallinity damage and rather occurred in amorphous regions of HA nanomaterial. In vitro tests based on the MG-63 cell line demonstrated that the introduction of Fe3+ does not cause cytotoxicity and led to the enhanced cytocompatibility of HA.
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