Engineering Mechanical, Biochemical, and Topographical Niche Cues by Photocrosslinkable, Microribbon-Like Hydrogels

Abstract

Extracellular matrix (ECM) influences cell fates via various kinds of ECM properties, including biochemical cues, microarchitectures, and matrix stiffness. Tissue engineering scaffolds have been created to approach the optimal ECM properties for desired cell behaviors, or to provide a biomaterials library to help understand how combinatorial effects of ECM properties affect cell fates and tissue formation. Given that cells often respond to the environments in a complex and unpredictable manner, scaffolds with easily tunable biochemical and biophysical properties are highly desirable. Current tissue engineering scaffolds, such as hydrogels and prefabricated bio-architectures, often provide limited tunability due to intertwined niche properties, lack of macroporosity, or the difficulty to reach uniform cell distribution. To overcome such limitations, we created microribbon-like, crosslinkable hydrogels as a new generation of scaffolding materials. Gelatin-based microribbons provide independently tunable macroporosity and matrix stiffness, as gelatin-based biochemical ligands promote cell adhesion and proliferation. PEG-based microribbons enable the independent control of macroporosity, matrix stiffness, and biochemical cues. Both types of microribbons support direct cell encapsulation in 3D, and allow uniform cell distribution with desired cell density, which facilitate the control of cell-cell interaction and rate of ECM production. The resulting macroporous scaffolds influence cell morphology and cell proliferation via independently tunable matrix stiffness, biochemical ligands, and macroporosity. The microribbons are highly versatile; in addition to controlling cell behaviors and tissue regeneration, these ribbon-like building blocks can be used as a biomaterials library to help elucidate the complex interactions between cell fates and ECM properties.