Polydopamine Interfacial Coating for Stable Tumor-on-a-Chip Models: Application for Pancreatic Ductal Adenocarcinoma.

ABSTRACT

Addressing current challenges in solid tumor research requires advanced in vitro three-dimensional (3D) cellular models that replicate the inherently 3D architecture and microenvironment of tumor tissue, including the extracellular matrix (ECM). However, tumor cells exert mechanical forces that can disrupt the physical integrity of the matrix in long-term 3D culture. Therefore, it is necessary to find the optimal balance between cellular forces and the preservation of matrix integrity. This work proposes using polydopamine (PDA) coating for 3D microfluidic cultures of pancreatic cancer cells to overcome matrix adhesion challenges to sustain representative tumor 3D cultures. Using PDA's distinctive adhesion and biocompatibility, our model uses type I collagen hydrogels seeded with different pancreatic cancer cell lines, prompting distinct levels of matrix deformation and contraction. Optimizing the PDA coating enhances the adhesion and stability of collagen hydrogels within microfluidic devices, achieving a balance between the disruptive forces of tumor cells on matrix integrity and the maintenance of long-term 3D cultures. The findings reveal how this tension appears to be a critical determinant in spheroid morphology and growth dynamics. Stable and prolonged 3D culture platforms are crucial for understanding solid tumor cell behavior, dynamics, and responses within a controlled microenvironment. This advancement ultimately offers a powerful tool for drug screening, personalized medicine, and wider cancer therapeutics strategies.