Dynamic matrix remodeling in boronate ester hydrogels for 3D organoid cultures

Abstract

This study demonstrates the development of a viscoelastic hydrogel-based matrix designed to promote physiological tissue microenvironment in 3D cell cultures, utilizing hyaluronic acid—a natural constituent of the extracellular matrix—as the primary polymer. The use of dynamic covalent chemistry, specifically boronate ester bonds, allows for the creation of a tunable biomimetic material with reversible bonds conducive to cell-mediated matrix remodeling. Poly(vinyl alcohol) was employed as cross-linker to form boronate ester bonds, while the polymerization of methacrylate moieties provided a covalently crosslinked network that further improved scaffold stability. Notably, the dynamic boronate ester containing hydrogels performed better than fully static ones, especially in terms of promoting cell proliferation. The hydrogel enabled successful encapsulation of kidney organoids (tubuloids) and intrahepatic cholangiocyte organoids (ICOs), demonstrating viability, increased proliferation compared to static gels, and self-organization into 3D structures. These results highlight the potential of dynamic boronate ester hydrogels, offering a promising step toward animal-free alternatives for organoid culture.