Abstract
Vessel morphogenesis is vital to regenerative medicine strategies. Here, collagen polymers, specified by intermolecular cross-link composition, are used to independently vary microstructure (fibril density, interfibril branching) and physical properties (stiffness) to guide 3D vessel network formation by endothelial colony forming cells (ECFC) in vitro. Increasing stiffness, by modulation of fibril density or interfibril branching, increases vessel diameter, length and branching. Oligomer matrices also induce vessel stabilization via type IV collagen deposition. This work shows that ECFC vessel formation depends on the interplay of collagen microstructure and physical properties and names oligomers and intermolecular cross-links as key design parameters for vascular-inductive matrices.