Instant assembly of collagen for tissue engineering and bioprinting

Abstract

Engineering functional cellular tissue components holds great promise in regenerative medicine. Collagen I, a key scaffolding material in bodily tissues, presents challenges in controlling its assembly kinetics in a biocompatible manner in vitro, restricting its use as a primary scaffold or adhesive in cellular biofabrication. Here we report a collagen fabrication method termed as tunable rapid assembly of collagenous elements that leverages macromolecular crowding to achieve the instant assembly of unmodified collagen. By applying an inert crowder to accelerate the liquid–gel transition of collagen, our method enables the high-throughput creation of physiological collagen constructs across length scales—from micro to macro—and facilitates cell self-assembly and morphogenesis through the generation of tunable multiscale architectural cues. With high biocompatibility and rapid gelation kinetics, the tunable rapid assembly of collagenous elements method also offers a versatile bioprinting approach for collagen over a wide concentration range, enabling the direct printing of cellular tissues using pH-neutral, bioactive collagen bioinks and achieving both structural complexity and biofunctionality. This work broadens the scope of controllable multiscale biofabrication for tissues across various organ systems using unmodified collagen.