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The formation of vascular outgrowths (sprouts) from cellular spheroids based on endotheliocytes and mesenchymal stromal cells was demonstrated to take place upon culturing the spheroids in a three-dimensional fibrin gel. The results can serve as a basis for a new angiogenesis model of a high biological relevance.

The review presents literature data on embryogenesis, physiological and reparative thyroid gland (TG) regeneration in the postnatal period in terms of substantiating the presence of stem/progenitor cells in its tissue. The data concerning genetic and protein markers of thyroid stem cells, as well as markers of their thyroid differentiation, are systematized. Unresolved problems and perspectives of the use of thyroid stem/progenitor cells in tissue engineering are discussed.

Calcium phosphate cements (CPCs) are advanced materials to fill bone tissue defects due to the complex of benefits [1, 2]. CPCs have a simple protocol of preparation and application, set under physiological conditions and exhibit osteoconductive properties. The bioresorption rate of brushite cements (BCs) is close to growth rate of bone de novo. The main lack of BCs is poor mechanical properties and acidosis of surrounding tissues during setting and hardening. Carbonated hydroxyapatite ceramics granules can be used to enhance mechanical characteristics of BCs and to stabilize pH values close to neutral of the BCs surrounding media, simultaneously. Moreover, to prevent deformations of BCs scaffolds, porous polylactide (PL) framework with Kelvin structure can be applied as reinforcement. Current investigation is focused on in vitro study of the BCs with the addition of carbonated hydroxyapatite (CHA) granules and reinforced by the porous polylactide frame.

Recent approaches to the calcium phosphate (CaP) materials functionalization with drugs and biomolecules have been actively developed for bone defect reconstruction. However, the current techniques are low efficient in context of drug incorporation and non-controlled release from the materials. Eventually, continuous therapeutic effect in bone defect area couldn’t be achieved. The aim of this work was to develop an effective method for biologically active molecules incorporation onto the surface of CаP materials, and to study the dynamics of its release. Octacalcium phosphate (OCP), β-tricalcium phosphate (β-TCP) and β-tricalcium phosphate with biomimetic calcium phosphate layer (β-TCPmod.) were used as ceramic bioactive carriers. Bovine serum albumin (BSA) was used as a model compounds. BSA incorporation on the ceramics surface was performed by biomimetic co-precipitation from several buffer solutions containing the incorporated compound. The efficiency of biomolecules incorporation was evaluated by measuring BSA concentrations in solutions before and after materials incubation. The release of the incorporated molecules from the materials was investigated for 6 days. The structure and composition of the obtained materials were studied by application of XRD, FTIR, SEM, BET methods. It was shown that the OCP specific surface (surface area, (SBET)) was almost in 12 times higher than SBET of β-TCP. By using biomimetic approach the increase of β-TCP surface area in 1.6 times was achieved; this enhanced protein incorporation more than 3 times. The BSA biomimetic co-precipitation together with CaP on the OCP surface proved to be more effective than its adsorption from salt free solutions. The study of BSA release revealed that only 45% of loaded albumin released during 6 days of observation. Therefore, the effective method of CaP functionalization was developed. Based on biomolecules incorporation by biomimetic co-precipitation from CaP solutions, it provided a low rate of its release., В последнее время активно разрабатываются подходы к функционализации кальцийфосфатных (КФ) материалов лекарственными препаратами и биологически активными соединениями с целью использования их в качестве платформы для адресной доставки в зону костного дефекта. Однако существующие технологии характеризуются низкой эффективностью инкорпорации и неудовлетворительной скоростью высвобождения препаратов из материалов, не обеспечивающей постоянный и длительный терапевтический эффект в области дефекта. Целью данной работы стала разработка эффективного способа функционализации КФ материалов биологически активными соединениями и изучение динамики их высвобождения. В работе использовали гранулированные КФ материалы октакальциевый фосфат (ОКФ), β-трикальциевый фосфат (β-ТКФ) и β-ТКФ с дополнительным КФ слоем на поверхности (β-ТКФмод.), а в качестве модельного соединения - бычий сывороточный альбумин (BSA). Инкорпорацию BSA на поверхность керамики производили совместно с биомиметическим осаждением из различных КФ буферных растворов, содержащих инкорпорируемое соединение. Эффективность инкорпорации BSA оценивали, измеряя его концентрации в растворах до и после инкубации с материалами. Динамику выхода BSA из материалов исследовали в течение 6 суток. Поверхность и структуру КФ материалов исследовали с помощью комплекса методов: сканирующей электронной микроскопии, рентгенофазового анализа, ИК-Фурье спектрального анализа, низкотемпературной адсорбции азота. В работе показано, что удельная площадь поверхности (Sуд.) ОКФ составила 5.9 м2/г, β-ТКФ – 0.5 м2/г. Модификация поверхности β-ТКФ привела к увеличению Sуд. в 1.6 раз и увеличению количества встроенного BSA на его поверхность в 3 раза. Совместная преципитация BSA и фосфатов кальция в процессе биомиметического осаждения была значительно эффективнее адсорбции BSA без использования КФ растворов. Исследование динамики высвобождения BSA из функционализированного ОКФ выявило, что в течение 6 суток наблюдения высвобождается 45% встроенного в материал белка. Таким образом, был разработан эффективный метод функционализации КФ материалов, основанный на инкорпорации биологически активных соединений совместно с биомиметическим осаждением из кальций- фосфатного раствора и обеспечивающий низкую скорость их высвобождения.

An association between the presence of the activated form of Ha-ras-1 and c-myc genes and increased cellular radioresistance has been shown in several cell lines. The aim of this study was to determine whether such an association could be observed in clinical tumour biopsies. We examined 70 tumour specimens and 51 samples of peripheral blood obtained from untreated patients with carcinoma of the uterine cervix mainly stage II and III. In addition to initial clinical tumour response to radiotherapy, radiosensitivity was also analysed by the subrenal capsule assay (SRCA). Mutations in exons 1 and 2 of the Ha-ras-1 gene were examined using PCR single-strand conformation polymorphism (PCR-SSCP) and direct sequencing; and restriction fragment length polymorphism of the Ha-ras-1 gene was analysed using Southern hybridisation. Eight (11%) out of 70 tumours contained mutations in exons 1 and 2 of the Ha-ras-1 gene. Eleven (22%) out of the 51 tumours displayed rearrangements of the Ha-ras-1 gene (six tumours (12%) showed alterations of allele length, one amplification and four (8%) loss of one Ha-ras-1 allele). In addition, 12 (17%) out of 70 patients demonstrated the presence of rare alleles. Only one of the 70 tumours contained an amplified c-myc gene. There was no significant correlation between either rearrangements of the structure of the Ha-ras-1 and/or c-myc genes or presence of rare alleles in tumours and tumour response to radiotherapy.