Granular Matrigel: restructuring a trusted extracellular matrix material for improved permeability

Abstract Matrigel is a polymeric extracellular matrix material produced by mouse cancer cells. Over the past four decades, Matrigel has been shown to support a wide variety of two- and three-dimensional cell and tissue culture applications including organoids. Despite widespread use, transport of molecules, cells, and colloidal particles through Matrigel can be limited. These limitations restrict cell growth, viability, and function and limit Matrigel applications. A strategy to improve transport through a hydrogel without modifying the chemistry or composition of the gel is to physically restructure the material into microscopic microgels and then pack them together to form a porous material. These ‘granular’ hydrogels have been created using a variety of synthetic hydrogels, but granular hydrogels composed of Matrigel have not yet been reported. Here we present a drop-based microfluidics approach for structuring Matrigel into a three-dimensional, mesoporous material composed of packed Matrigel microgels, which we call granular Matrigel. We show that restructuring Matrigel in this manner enhances the transport of colloidal particles and human dendritic cells (DCs) through the gel while providing sufficient mechanical support for culture of human gastric organoids (HGOs) and co-culture of human DCs with HGOs.