Abstract
Hierarchical molecular assembly directed by cell-regulated aqueous solvent is a fundamental strategy for manufacturing various proteinaceous structures that are of intense interest for nanotechnology, sustainable manufacturing and regenerative medicine. However, to translate the natural strategy into advanced digital manufacturing like three-dimensional (3D) printing remains a tremendous technical and theoretical challenge. This work presents a 3D printing technique of a particular protein, silk fibroin, by rationally designing an de novo aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and remarkable mechanical performance. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. Exceptional manufacturing capability and one promising application is exemplified by the single-step construction of perfusable microfluidic chips, also an analogy of small-diameter vascular grafts, which eliminates the use of supporting or sacrificial materials owing to optimized crosslinking dynamics and compartmentalized printing parameters. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds.