Остеопластические материалы нового поколения на основе биологических и синтетических матриксов

Objectives. The purpose of this analytical review is to evaluate the market for osteoplastic materials and surgical implants, as well as study the features of new-generation materials and the results of clinical applications.Methods. This review summarizes the volumes of research articles presented in the electronic database PubMed and eLIBRARY. A total of 129 scientific articles related to biological systems, calcium phosphate, polymer, and biocomposite matrices as carriers of pharmaceutical substances, primary recombinant protein osteoinductors, antibiotics, and biologically active chemical reagents were analyzed and summarized. The search depth was 10 years.Results. Demineralized bone matrix constitutes 26% of all types of osteoplastic matrices used globally in surgical osteology, which includes neurosurgery, traumatology and orthopedics, dentistry, and maxillofacial and pediatric surgery. Among the matrices, polymer and biocomposite matrices are outstanding. Special attention is paid to the possibility of immobilizing osteogenic factors and target pharmaceutical substances on the scaffold material to achieve controlled and prolonged release at the site of surgical implantation. Polymeric and biocomposite materials can retard the release of pharmaceutical substances at the implantation site, promoting a decrease in the toxicity and an improvement in the therapeutic effect. The use of composite scaffolds of different compositions in vivo results in high osteogenesis, promotes the initialization of biomineralization, and enables the tuning of the degradation rate of the material.Conclusions. Osteoplastic materials of various compositions in combination with drugs showed accelerated regeneration and mineralization of bone tissue in vivo, excluding systemic side reactions. Furthermore, although some materials have already been registered as commercial drugs, a plethora of unresolved problems remain. Due to the limited clinical studies of materials for use on humans, there is still an insufficient understanding of the toxicity of materials, time of their resorption, speed of drug delivery, and the possible long-term adverse effects of using implants of different compositions.Цели. Цель литературного обзора – анализ остеопластических материалов и хирургических имплантатов нового поколения, изучение особенностей, характеристик и результатов их клинического применения.Методы. Обзор суммирует объем научно-исследовательских материалов, представленных на порталах «PubMed» и «eLIBRARY». Проанализирован и обобщен материал 129 научных статей по следующим разделам: биологические, кальций-фосфатные, полимерные и биокомпозитные матриксы в качестве носителей целевых фармацевтических субстанций (рекомбинантных белковых остеоиндукторов, антибиотиков и биологически активных химических реагентов). Глубина поиска 10 лет.Результаты. Среди всех видов остеопластических матриксов, применяемых в настоящее время в мировой хирургической остеологии, куда входит нейрохирургия, травматология и ортопедия, стоматология, челюстно-лицевая и детская хирургия, деминерализованный костный матрикс (ДКМ) занимает 26%. Полимерные и биокомпозитные матриксы сегодня представляются наиболее перспективными материалами в сравнении с ДКМ. Особое внимание в разработке новых видов матриксов уделяется возможности фиксации остеогенных факторов и целевых фармацевтических субстанций на материале-носителе с целью их контролируемого и пролонгированного выпуска на участке хирургической имплантации. Полимерные и биокомпозитные материалы способны замедлять время высвобождения фармсубстанций в месте имплантации, способствуя снижению токсичности и пролонгации терапевтического эффекта, являясь перспективной альтернативой аутогенной кости. Использование композитных носителей различного состава in vivo демонстрирует высокие показатели остеогенеза, способствует запуску биоминерализации и позволяет варьировать скорость деградации материала.Выводы. Остеопластические материалы различного состава в сочетании с лекарственными средствами показали ускорение регенерации и минерализации костной ткани in vivo, исключая системные побочные реакции. И, хотя некоторые материалы уже зарегистрированы в качестве коммерческих препаратов, все еще сохраняется ряд нерешенных проблем. Из-за ограниченности клинических исследований материалов на людях остаются открытыми такие вопросы как недостаточное понимание токсичности материалов, времени их резорбции, скорости доставки лекарственного средства и его высвобождения, а также возможные неблагоприятные эффекты от использования имплантатов различного состава

Peasant settlers and the ‘civilizing mission’ in Russian Turkestan, 1865-1917

This article provides an introduction to one of the lesser-known examples of European settler colonialism, the settlement of European (mainly Russian and Ukrainian) peasants in Southern Central Asia (Turkestan) in the late nineteenth and early twentieth centuries. It establishes the legal background and demographic impact of peasant settlement, and the role played by the state in organising and encouraging it. It explores official attitudes towards the settlers (which were often very negative), and their relations with the local Kazakh and Kyrgyz population. The article adopts a comparative framework, looking at Turkestan alongside Algeria and Southern Africa, and seeking to establish whether paradigms developed in the study of other settler societies (such as the ‘poor white’) are of any relevance in understanding Slavic peasant settlement in Turkestan. It concludes that there are many close parallels with European settlement in other regions with large indigenous populations, but that racial ideology played a much less important role in the Russian case compared to religious divisions and fears of cultural backsliding. This did not prevent relations between settlers and the ‘native’ population deteriorating markedly in the years before the First World War, resulting in large-scale rebellion in 1916

Heparin-Induced Changes of Vascular Endothelial Growth Factor (VEGF₁₆₅) Structure

Vascular endothelial growth factor-A (VEGF-A), a secreted homodimeric glycoprotein, is a critical regulator of angiogenesis in normal and pathological states. The binding of heparin (HE) to VEGF165 (the major form of VEGF-A) modulates the angiogenesis-related cascade, but the mechanism of the observed changes at the structural level is still insufficiently explored. In the present study, we examined the effect of HE on the structural and physicochemical properties of recombinant human VEGF165 (rhVEGF165). The HE binding results in an increase of hydrophobic surface exposure in rhVEGF165 without changes in its secondary structure. Differential scanning calorimetry measurements for intact and HE-bound rhVEGF165 reveals the absence of any pronounced thermally induced transitions in the protein in the temperature range from 20 to 100 °C. The apolar area increase during the heparin binding explains the pronounced HE-induced oligomerization/aggregation of rhVEGF165, as studied by chemical glutaraldehyde cross-linking and dynamic light scattering. Molecular modeling and docking techniques were used to model the full structure of dimeric VEGF165 and to reveal putative molecular mechanisms underlying the function of the VEGF165/HE system. In general, the results obtained can be a basis for explaining the modulating effect of HE on the biological activity of VEGF-A

Comparison of Spatial Structures and Packaging of Phosphorybosil Pyrophosphate Synthetase 2 from Thermus thermophilus HB27 in Rhombohedral and Tetragonal Crystals

We report the spatial structure of phosphoribosyl pyrophosphate synthetase 2 from the thermophilic bacterium Thermus thermophilus HB27 (TthPRPPS2) obtained at a 1.85 Å resolution using a diffraction set collected from rhombohedral crystals (space group R32-h), grown with lithium sulfate as a precipitant. This crystal structure was compared with the structure of TthPRPPS2, previously obtained at a 2.2 Å resolution using diffraction sets from the tetragonal crystals (space group P41212), grown with ammonium sulfate as a precipitant. The comparison of these structures allows the study of the differences between protein molecules in both crystalline structures, as well as the packaging of enzyme molecules in crystals of both spatial groups. Our results may contribute to the research of the structural basis of catalytic activity and substrate specificity of this enzyme

“Applied Orientalism” in British India and Tsarist Turkestan

‘We cannot promise to those who may choose Oriental scholarship, that they shall find themselves abreast, in all the various high-roads of life which lead to profit and distinction, with the men who shall have devoted themselves to acquiring the knowledge which in these days is power, the intellectual treasures which make fifty years of Europe better than a cycle in Cathay, which are the sinews of peaceful empire as surely as money is the sinew of war.

Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro

The success in treatment of venous thromboembolism and acute coronary syndromes using direct thrombin inhibitors has stimulated research aimed at finding a new anticoagulant from haematophagous organisms. This study deals with the comparison between hirudin-1 from Hirudomedicinalis(desirudin), being the first-known and most well-studied natural anticoagulant, along with recombinant analogs of haemadin from the leech Haemadipsa sylvestris, variegin from the tick Amblyomma variegatum, and anophelin from Anopheles albimanus. These polypeptides were chosen due to their high specificity and affinity for thrombin, as well as their distinctive inhibitory mechanisms. We have developed a universal scheme for the biotechnological production of these recombinant peptides as pharmaceutical substances. The anticoagulant activities of these peptides were compared using the thrombin amidolytic activity assay and prolongation of coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time) in mouse and human plasma. The preliminary results obtained suggest haemadin as the closest analog of recombinant hirudin-1, the active substance of the medicinal product Iprivask (Aventis Pharmaceuticals, USA) for the prevention of deep venous thrombosis in patients undergoing elective hip or knee replacement surgery. In contrast, variegin can be regarded as a natural analog of bivalirudin (Angiomax, The Medicines Company), a synthetic hirudin-1 derivative certified for the treatment of patients undergoing percutaneous coronary intervention and of patients with unstable angina pectoris after percutaneous transluminal coronary angioplasty