Silk biomaterials in the era of digital manufacturing: Physics, processing, and biomedical translation

Additive manufacturing has gained prominence as a powerful platform for fabricating morphologically complex and functionally active biomaterial constructs for biomedical applications. Among biopolymers, silk has been extensively explored owing to its good mechanical properties (tensile strength 300–740 MPa, Young's modulus 5–17 GPa, toughness ∼70 MJ/m3), degradation behavior, rich functional bioactive groups, and aqueous processability. However, translating silk into printable bioinks is limited by its inherent structural hierarchy and sensitivity to processing conditions. This review provides a critical overview of the properties and processing of silk in light of Digital manufacturing, with emphasis on structure, properties, functionalization, and printability. Moreover, the effects of different degumming methods and functionalization protocols on the rheological properties of silk solutions are analyzed. The resulting implications for printing fidelity are also examined, demonstrating that processing-derived molecular and conformational changes critically determine flow behavior, shape retention, and structural resolution in 3D-printed constructs. State-of-the-art developments in extrusion-based, inkjet, and light-assisted printing techniques for silk-based systems are systematically evaluated, including cross-linking mechanisms, composite formulations, and post-printing analyses, depending on the desired application focus. Moreover, the influence of printing parameters on filament formation, hierarchical organization, and mechanical and functional performance is thoroughly discussed. Crucially, biomedical applications of 3D printed silk constructs spanning from tissue engineering scaffolds, and drug delivery systems to biosensors are reviewed, emphasizing design-function correlation. Thus, this review positions silk as a versatile material for next-generation digital manufacturing and biofabrication.