Razvoj novih metod izdelave in karakterizacije mikrožilja v in vitro modelih

Vajda, Jernej

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Title:	Razvoj novih metod izdelave in karakterizacije mikrožilja v in vitro modelih
Authors:	ID Vajda, Jernej (Author) ID Maver, Uroš (Mentor) More about this mentor... ID Vihar, Boštjan (Comentor)
Files:	DOK_Vajda_Jernej_2025.pdf (52,49 MB) MD5: 0076AEFE456E76986A50C419A0B2F0BF
Language:	Slovenian
Work type:	Dissertation
Typology:	2.08 - Doctoral Dissertation
Organization:	MF - Faculty of Medicine
Abstract:	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.
Keywords:	mikrožilje, in vitro model, 3D tisk, računalniška dinamika tekočin, nanotomografija
Place of publishing:	Maribor
Publisher:	[J. Vajda]
Year of publishing:	2025
PID:	20.500.12556/DKUM-92988
UDC:	611.16+612.014.2:616-003.93:0041.356(043.3)
COBISS.SI-ID:	238388483
Publication date in DKUM:	04.07.2025
Views:	188
Downloads:	61
Metadata:
Categories:	MF
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	29.05.2025

Secondary language

Language:	English
Title:	Development of new fabrication and characterization methods of microvasculature in in vitro models
Abstract:	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.
Keywords:	microvasculature, in vitro model, 3D printing, computational fluid dynamics, nanotomography

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