FEATURES OF PREOPERATIVE MANAGEMENT AND METHODS OF EXAMINATION OF PATIENTS OF GROUPS UNDER RESEARCH

Despite the active ability to repair, it is frequently noticed that the independent potentialof bone tissue is insufficient, that is a serious problem in reconstructive maxillofacialsurgery, orthopedics and traumatology. In recent years, there has been an activesearch for implant material that would match the autologous bone in its properties andcharacteristics. Tissue engineering technologies allow to create tissue equivalents tobone tissue using autogenous stromal cells deposited on biocompatible or biologicalmaterial of tissue engineering design. The article presents the features of preoperativemanagement, description of the used examination methods and bone augmentationmaterials in patients of the groups under study.Objective – to use a set of adequate methods of examination and optimal preoperativemanagement of patients of the group under study during sinus lifting, post-extractionsocket preservation, osteosynthesis for mandibular fractures and impacted wisdom teethextraction, which were accompanied by the use of bone augmentation materials based onmultipotent mesenchymal stromal cells.Material and methods. 280 people aged 18 to 55 with partial or complete adentiaand atrophy of the alveolar process of the jaws, with chronic periodontium infectionand chronic generalized periodontitis, with fractures and impacted third molars wereexamined in the Department of Surgical Dentistry and Maxillofacial Surgery of theChernivtsi Regional Clinical Hospital. All patients were planned to make orthopedicstructures based on dental implants.Results. The use of computed tomography in preoperative examination of patients in thestudied group allows not only visually to examine the object, but also to perform directdensitometric analysis with measurement of attenuation coefficients in Hounsfield units,that is a significant advantage over X-ray examination.Conclusions. The use of bone augmentation materials based on multipotent mesenchymalstromal cells of adipose tissue during dental operations improves the regenerativeproperties of bone tissue and helps to reduce the duration of inpatient treatment.

Controlling fibroblast fibrinolytic activity allows for the bio-engineering of stable connective tissue equivalents

In tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degradative fibroblasts through the secretion of fibrinolytic matrix-metalloproteinases (MMPs) and urokinase, two types of serine protease. Finally, we demonstrated that besides aprotinin, specific targeting of fibrinolytic MMPs and urokinase led to cell-laden GAF stability for at least several days. These results support the use of specific strategies to tune fibrin-based biomaterials degradation over time. It emphasizes the need to choose the right cell type and further bring targeted solutions to avoid the degradation of fibrin-containing hydrogels or bioinks.

3D bioprinting: novel approaches for engineering complex human tissue equivalents and drug testing

Conventional approaches in drug development involve testing on 2D-cultured mammalian cells, followed by experiments in rodents. Although this is the common strategy, it has significant drawbacks: in 2D cell culture with human cells, the cultivation at normoxic conditions on a plastic or glass surface is an artificial situation that significantly changes energy metabolism, shape and intracellular signaling, which in turn directly affects drug response. On the other hand, rodents as the most frequently used animal models have evolutionarily separated from primates about 100 million years ago, with significant differences in physiology, which frequently leads to results not reproducible in humans. As an alternative, spheroid technology and micro-organoids have evolved in the last decade to provide 3D context for cells similar to native tissue. However, organoids used for drug testing are usually just in the 50–100 micrometers range and thereby too small to mimic micro-environmental tissue conditions such as limited nutrient and oxygen availability. An attractive alternative offers 3D bioprinting as this allows fabrication of human tissue equivalents from scratch with hollow structures for perfusion and strict spatiotemporal control over the deposition of cells and extracellular matrix proteins. Thereby, tissue surrogates with defined geometry are fabricated that offer unique opportunities in exploring cellular cross-talk, mechanobiology and morphogenesis. These tissue-equivalents are also very attractive tools in drug testing, as bioprinting enables standardized production, parallelization, and application-tailored design of human tissue, of human disease models and patient-specific tissue avatars. This review, therefore, summarizes recent advances in 3D bioprinting technology and its application for drug screening.

Modeling SARS-CoV-2 and Influenza Infections and Antiviral Treatments in Human Lung Epithelial Tissue Equivalents

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third coronavirus in less than 20 years to spillover from an animal reservoir and cause severe disease in humans. High impact respiratory viruses such as pathogenic beta-coronaviruses and influenza viruses, as well as other emerging respiratory viruses, pose an ongoing global health threat to humans. There is a critical need for physiologically relevant, robust and ready to use, in vitro cellular assay platforms to rapidly model the infectivity of emerging respiratory viruses and discover and develop new antiviral treatments. Here, we validate in vitro human alveolar and tracheobronchial tissue equivalents and assess their usefulness as in vitro assay platforms in the context of live SARS-CoV-2 and influenza A virus infections. We establish the cellular complexity of two distinct tracheobronchial and alveolar epithelial air liquid interface (ALI) tissue models, describe SARS-CoV-2 and influenza virus infectivity rates and patterns in these ALI tissues, the viral-induced cytokine production as it relates to tissue-specific disease, and demonstrate the pharmacologically validity of these lung epithelium models as antiviral drug screening assay platforms.

Hyaluronic Acid as Macromolecular Crowder in Equine Adipose-Derived Stem Cell Cultures

The use of macromolecular crowding in the development of extracellular matrix-rich cell-assembled tissue equivalents is continuously gaining pace in regenerative engineering. Despite the significant advancements in the field, the optimal macromolecular crowder still remains elusive. Herein, the physicochemical properties of different concentrations of different molecular weights hyaluronic acid (HA) and their influence on equine adipose-derived stem cell cultures were assessed. Within the different concentrations and molecular weight HAs, the 10 mg/mL 100 kDa and 500 kDa HAs exhibited the highest negative charge and hydrodynamic radius, and the 10 mg/mL 100 kDa HA exhibited the lowest polydispersity index and the highest % fraction volume occupancy. Although HA had the potential to act as a macromolecular crowding agent, it did not outperform carrageenan and Ficoll®, the most widely used macromolecular crowding molecules, in enhanced and accelerated collagen I, collagen III and collagen IV deposition.

Mechanical homeostasis in tissue equivalents: a review

There is substantial evidence that growth and remodeling of load bearing soft biological tissues is to a large extent controlled by mechanical factors. Mechanical homeostasis, which describes the natural tendency of such tissues to establish, maintain, or restore a preferred mechanical state, is thought to be one mechanism by which such control is achieved across multiple scales. Yet, many questions remain regarding what promotes or prevents homeostasis. Tissue equivalents, such as collagen gels seeded with living cells, have become an important tool to address these open questions under well-defined, though limited, conditions. This article briefly reviews the current state of research in this area. It summarizes, categorizes, and compares experimental observations from the literature that focus on the development of tension in tissue equivalents. It focuses primarily on uniaxial and biaxial experimental studies, which are well-suited for quantifying interactions between mechanics and biology. The article concludes with a brief discussion of key questions for future research in this field.

Оценка жизнеспособности живых тканевых эквивалентов под действием импульсного тока со смещением

The paper deals with an electrophysical device for combined electroporative-iontophoretic effect on biological membranes. The experimental results on the influence of a pulsed current source with displacement on the viability of living tissue equivalents (LTE) cells are presented. There were obtained values ​​of pulse electrophysical parameters providing preservation of LTE cell vitality. According to the obtained data we suggest that such electrophysical parameters can be used for drugs delivery through the equivalent of the round window membrane and for creation in the future a technology for the administration of drugs through biological barriers with the possibility of their penetration into the inner ear using pulsed electrical installations.