20.500.12556/DKUM-92988 Razvoj novih metod izdelave in karakterizacije mikrožilja v in vitro modelih Development of new fabrication and characterization methods of microvasculature in in vitro models Doktorska disertacija obravnava optimizacijo postopkov, materialov in analiznih metod v tkivnem inženirstvu mikrožilja z multidisciplinarnim pristopom, ki poleg uveljavljenih bioloških in kemijskih metod vključuje tudi računalniške simulacije, mehanske teste in nanotomografijo. V okviru raziskovalnega dela smo optimizirali linearnost ekstruzije mehanskih ekstruzijskih 3D tiskalnikov, s čimer smo dosegli boljše in bolj ponovljive rezultate 3D (bio)tiska vzorcev. Pri natisnjenih vzorcih smo primerjali uporabo CaCl2 in SrCl₂ kot ionskih zamreževalcev, pri čemer se je izkazalo, da je uporaba SrCl2 ob primerljivi celični metabolni aktivnosti izboljšala mehanske lastnosti materialov, kombinacija Sr²⁺ in Ca²⁺ pa bi lahko omogočala dodatno prilagoditev mehanskih lastnosti materialov. Uporaba Sr²⁺ hkrati zmanjša tudi vpliv kalcijevih ionov na signalizacijo celic, kar je ključno za simuliranje biološkega okolja. Na drugi strani smo s simulacijami računalniške dinamike tekočin določili mejne pogoje za razvoj peristaltične črpalke, s katero smo eksperimentalno ovrednotili vpliv strižnih napetosti na endotelijske celice in validirali simulirane rezultate. Ločeno smo na endotelijskih celicah iz različnih virov in na podpornih celicah – kožnih fibroblastih – preiskovali lastnosti materialov in njihov vpliv na viabilnost, ohranitev celičnega fenotipa in funkcionalnosti ter celokupno metabolno aktivnost. Rezultati študij potrjujejo, da je z natančno optimizacijo procesov in materialov mogoče izboljšati funkcionalnost tkivnih in vitro modelov, kar odpira nove možnosti za napredek v tkivnem inženirstvu in regenerativni medicini. The doctoral dissertation addresses the optimization of processes, materials, and analytical methods in tissue engineering of microvasculature using a multidisciplinary approach. This approach incorporates established biological and chemical methods as well as computational simulations, mechanical testing, and nanotomography. In the scope of the work, we optimized the linearity of extrusion in mechanical extrusion-based 3D printers, achieving better and more reproducible results in 3D (bio)printing. For the printed samples, we compared the use of CaCl₂ and SrCl₂ as ionic crosslinkers, finding that the use of SrCl₂ improved the mechanical properties of the materials while maintaining comparable cellular metabolic activity. Furthermore, the combination of Sr²⁺ and Ca²⁺ ions could allow for additional tailoring of the mechanical properties of the materials, while reducing the impact of calcium ions on cell signaling, the latter being crucial for simulating biological environments. On another front, through computational fluid dynamics simulations, we determined the boundary conditions for developing a peristaltic pump, which was experimentally used to evaluate the effect of shear stress on endothelial cells and validate the simulated results. Separately, we investigated the properties of materials and their impact on cell viability, retention of cellular phenotype and functionality, as well as overall metabolic activity, in endothelial cells from different sources and supportive cells – dermal fibroblasts. The research findings confirm that precise optimization of processes and materials can improve functionality of in vitro tissue models, paving the way for advancements in tissue engineering and regenerative medicine. mikrožilje in vitro model 3D tisk računalniška dinamika tekočin nanotomografija microvasculature in vitro model 3D printing computational fluid dynamics nanotomography true true false [J. Vajda] Slovenski jezik Angleški jezik Doktorska disertacija 2025-05-29 13:31:10 2025-07-04 08:39:49 2025-07-05 03:07:50 0000-00-00 00:00:00 2025 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 611.16+612.014.2:616-003.93:0041.356(043.3) 238388483 DOK_Vajda_Jernej_2025.pdf DOK_Vajda_Jernej_2025.pdf 1 0076AEFE456E76986A50C419A0B2F0BF 004ac95f0ea2fa1db47566de7ce815cca28b5a3d92d9e3b119c74aabe0304259 756ffc58-3c91-11f0-b9c3-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=191509 Medicinska fakulteta 0 0 0