Project R-15207

Applying dissociative chemistry to obtain anisotropic hydrogels (Research)

Gradients play an important role in the development, functioning and pathology of the human body. In cancer, the mechanical properties of the extracellular matrix (ECM) in the vicinity of the developing tumour is linked to malignancy. Realistic in vitro models that take this anisotropy into account allow us to increase our understanding of the metabolic processes in cancer and to test new drugs. To obtain such materials, various methodologies are being investigated to obtain anisotropic biomaterials that better mimic the ECM. However, the formation of stable, continuous stiffness gradients in biomaterials remains challenging. This project will apply the concept of dissociative bioorthogonal chemistry to yield hydrogels that can be selectively degraded following the diffusion of a cleavage agent into the hydrogel. To test this hypothesis, tetrazine-based cross-linkers will be synthesised and applied in the formation of PEG-based hydrogels. Next, the tetrazines will be partially degraded along the concentration gradient of an introduced isonitrile cleavage agent. The materials will be characterised in depth on a molecular and macroscopic scale. Finally, the hydrogels will be applied as scaffold in in vitro models of pancreatic cancer to study the effect stiffness gradients have on the developing tumour spheroids.

01 November 2024 - 31 October 2028