DEVELOPMENT OF BIOINSPIRED HYDROGEL CULTURE SYSTEMS FOR IN VITRO RECAPITULATION OF 3D TUMOR MICROENVIRONMENT

Date

2025-8-25

Author

Aydın, Hakan Berk

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The tumor microenvironment (TME) is based on the modification of the extracellular matrix (ECM), the main component of tissue structures, including both biomechanical and biochemical modifications during tumorigenesis. Mimicking the extracellular matrix plays a crucial role in modern biomedical and translational research. These animal-derived biomaterials are limited in their tunability and reproducibility, both because their use requires harvesting from animals and because they quickly reach their limits when using bottom-up, high-precision mimicry of the TME. To overcome this limitation, engineered matrices by combining synthetic and/or natural biomaterials have become the next generation of 3D tissue engineering approaches. This thesis aims to design and optimize hydrogel systems to mimic the TME with the tunability of biomechanical and biochemical properties for implementation into 3D cell culture methods, such as spheroid formation, via supporting cell survival, proliferation, and creating 3D structures. As well as to develop 3D hydrogel systems that reduce or eliminate reliance on typical commercially available animal-based biomaterials that have been used for 3D culture. Efforts have been made to incorporate two approaches, one focused on sodium alginate (ionic cross-linking) by itself or in combination with collagen (resulting in an interpenetrating network) and another focused on PEG4MAL (covalent crosslinking) with thiolated gelatin for functionalization. These developed hydrogel systems showed that they support proliferation of breast cancer and related stromal cells, can be used as a spheroid generation platform with changing stiffness, and allow investigation of the effect of microenvironmental cues in atorvastatin drug screening. In addition, since repurposed drug studies with statins are still very limited, we carried out experiments in 3D hydrogel systems and observed that atorvastatin was effective against breast cancer spheroids.

Subject Keywords

Tümör mikroçevresi, Statin, Kanser, Hidrojeller, Biyomalzemeler, TME, Tumor microenvironment, Cancer

URI

https://hdl.handle.net/11511/115693

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Graduate School of Natural and Applied Sciences, Thesis