Design and development of a microfluidic device for immune cell and patient-derived Hydrogel integration in a 3D colorectal cancer model

Colorectal cancer (CRC) is a significant global health challenge with high mortality, making the development of translatable preclinical models crucial for drug discovery. While three-dimensional in vitro cell culture systems are highly relevant, many rely on synthetic or animal-derived scaffolds that fail to accurately mimic human tissue biology. In contrast, hydrogels formulated from human decellularized extracellular matrix (dECM) retain vital native tissue-specific signals, offering a more physiologically relevant microenvironment for tumor cells. This research aimed to establish a robust 3D in vitro model that faithfully recapitulates the CRC tumor microenvironment (TME). The investigation focused on the interplay between a patient-derived dECMHydrogel and a stabilized monocytic cell line, which was further developed by integrating CRC patient-derived organoids (PDOs) into a co-culture system. To this end, THP-1 monocytic cells were cultured within either the dECMHydrogel or a commercial scaffold. Functional characteristics and the biocompatibility of both monocytes and CRC PDOs were investigated. In the developed co-culture model, assessments included cell viability and the response to treatment with 5-fluorouracil (5-FU).