Modulating Fibrillogenesis Enhances the Biofunctionality of Dense Collagen Hydrogels

Collagen type I underpins a wide range of biomaterials, yet conventional collagen hydrogels lack the mechanical strength required for translational applications, while densification strategies often compromise cellular accessibility. Here, we present a cell-compatible densification platform based on absorptive deformation (AD) that enables the fabrication of dense collagen sheets (DCSs) with tunable fibrillar architecture. By modulating fibrillogenesis prior to densification using ionic, macromolecular, and extracellular matrix-derived additives, we control fibril diameter, fibrillar bundling and interfibrillar spacing during fibrillogenesis. We demonstrate the versatility of this platform across biological contexts: hyaluronic acid-modulated DCSs support physiologically organised epithelial growth ex vivo, while ionically modulated DCSs promote enhanced host cell infiltration and early vascular interaction in vivo without inducing chronic inflammation. Together, this work establishes pre-densification control of fibrillogenesis as a strategy to engineer dense, biologically permissive collagen matrices, enabling structurally and functionally optimised scaffolds for tissue modelling and regenerative repair.