University of Twente Student Theses


Development of Bio-inspired Hydrogels with Tunable Viscoelastic Properties for 3D Cell Culture

Nasseri, Elham (2023) Development of Bio-inspired Hydrogels with Tunable Viscoelastic Properties for 3D Cell Culture.

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Abstract:Within the field of tissue engineering, there is a growing interest in the development of three-dimensional (3D cell culture models for various applications. These artificial models closely recapitulate the cellular microenvironment of native tissues, in contrast to two-dimensional (2D) models, which makes them crucial tools in cell biology research, for example, allowing to study and understand the principles of complex cell-matrix interactions. For the appropriate design of 3D cell culture models, the ability to replicate the cellular niche is crucial. The extracellular matrix (ECM), a 3D network around living cells, presents biochemical and biophysical cues across diverse length and time scales. It thereby offers structural support and facilitates cellular communication. The regulation of cellular functions and behavior is tightly regulated by this native ECM. It is becoming increasingly clear that the ECM’s mechanical characteristics, such as stiffness and viscoelasticity, play a significant role in controlling cell functions and fate. To recapitulate the characteristics of ECM into artificial tissues, synthetic biomaterials based on highly hydrated 3D polymeric crosslinked networks, called hydrogels, have been used extensively as tissue mimics throughout the past few decades, offering stable scaffolds for 3D cell culture. Despite the considerable progress achieved in the past 2-3 decades, a majority of engineered hydrogels still lack the dynamic essence inherent to the ECM environment. They primarily manifest as macroscopic adjustments to scaffold mechanics. Therefore, there is a need for more functional and biomimetic hydrogel designs, which can be more physiologically relevant with respect to the native tissues. One way of designing dynamic and adaptable networks is through the introduction of reversible crosslinks, especially those based on dynamic covalent bonds. In this context, a few dynamic covalent chemistries has been investigated which they used for cell encapsulation, but most of them lack fast dynamicity, convenient stability for cell culture applications or are weak in binding. In this project, we used a recently discovered bio-inspired dynamic covalent chemistry based on thiol groups to impart network dynamicity, and for higher stability of derived materials this was integrated with a static photo-crosslinking mode, which overall led to a novel hybrid hydrogel design. In order to develop a hybrid hydrogel platform with adjustable viscoelasticity, well-suited for 3D cell encapsulation, each hydrogel system (static, dynamic, and hybrid hydrogels) were characterized by conducting rheological studies and at the end preliminary cell encapsulation studies were conducted. Altogether, this research opens up the possibility of developing a promising, novel bio-inspired hydrogel platform characterized by innovative chemistries and adjustable viscoelastic properties. This platform is tailored for applications in 3D cell encapsulation models, representing a significant step towards expanding the current chemical toolkit for dynamic covalent chemistries suitable for bioengineering.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:35 chemistry, 42 biology, 51 materials science
Programme:Biomedical Engineering MSc (66226)
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