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Doctoral dissertation

Viscoelastic properties of hydrogel-based materials for tissue engineering scaffolds

Author(s): Rok Kocen (Author), Saša Novak (Supervisor)

Thesis defense date: 27.11.2017

Organization: MPŠ - Mednarodna podiplomska šola Jožefa Stefana

PID: 20.500.12556/ReVIS-14827

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Abstract

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Tissue engineering is an interdisciplinary field that combines medicine, biology, materials science, engineering, and other disciplines. Its goal is to help patients who have suffered tissue loss or damage by providing treatments that support and/or improve tissue regeneration. Such treatments may involve stem cells, cell scaffolds, and/or growth factors.
Scaffolds provide a suitable environment for stem cells to grow and for newly formed tissue to develop. They also provide stimuli for tissue growth and eventually degrade. More specifically, scaffolds need to be porous to provide space for stem cells to grow and allow bodily fluids to flow through them, supplying nutrients that enable cells to survive, differentiate, and proliferate. As cells multiply and new tissue grows, the scaffolds need to provide additional space; therefore, they should degrade. In addition, scaffolds must possess suitable mechanical properties to withstand mechanical loads.
The mechanical properties of scaffolds, both during preparation and throughout their use, must provide adequate support for stem cells. Most tissues and organs exhibit complex viscoelastic properties due to their high water content and protein matrix. Therefore, it is reasonable for scaffolds to exhibit a similar mechanical response. The most common materials currently used for scaffolds are hydrogels, which resemble many natural tissues because they contain more than 90% water held within a polymer network.
In this work, we investigated the viscoelastic properties of potential scaffold materials. The material used was gellan gum (GG) combined with bioactive glass (BAG) particles to promote bioactivity. Five techniques were evaluated using composite samples of GG and BAG. We determined that dynamic mechanical analysis (DMA) and rheometry were the most suitable techniques for fully characterising these viscoelastic hydrogel composites at physiologically relevant frequencies. Uniaxial compression also yielded comparable results, but provided less information on frequency dependence and damping properties. Indentation and ultrasonic wave propagation techniques were found to be unsuitable for characterising these hydrogel composites.
The mechanical properties of the samples were measured while they were immersed in simulated body fluid (SBF). We expected the samples to degrade after one month of immersion; however, they remained too stable to exhibit degradation. Nevertheless, noticeable hydroxyapatite formation was observed. Hydroxyapatite is the main mineral phase found in bone. After one month of immersion in SBF, the samples exhibited an increase in their viscoelastic properties.
Gellan gum was also investigated for 3D printing, which is a prerequisite for the practical application of personalised scaffolds. After studying the rheological properties of GG, we identified its potential for 3D printing. We modified a commercial 3D printer to enable it to process thermoactive hydrogels and successfully printed simple geometries using GG hydrogel.

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