Microstructured silk-fiber scaffolds with enhanced stretchability

Abstract

Despite extensive research, current methods for creating three-dimensional (3D) silk fibroin (SF) scaffolds lack control over molecular rearrangement, particularly in the formation of β-sheet nanocrystals, as well as hierarchical fiber organization at both micro- and macroscale. In this study, we introduce a fabrication process based on electrowriting of aqueous SF-based solutions followed by post-processing using an aqueous solution of sodium dihydrogen phosphate (NaH2PO4). This approach enables hierarchical assembly of SF chains via β-sheet and α-helix formation. Moreover, this process allows for precise control over micro- and macro-architectures in microfiber scaffolds, enabling the creation of 3D flat and tubular macrogeometries with square-based and crosshatch microarchitectures, featuring inter-fiber distances of 400 μm and approximately 97% open porosity. Remarkably, the printed structures demonstrated restored β-sheet and α-helix structures, which imparted an elastic response of up to 20% deformation and the ability to support cyclic loading without plastic deformation. Furthermore, the printed constructs supported in vitro adherence and growth of human conditionally immortalized proximal tubular epithelial cells and glomerular endothelial cells, with cell viability above 95%. These cells formed uniform, aligned monolayers that deposited their own extracellular matrix. These findings represent a significant development in fabricating organized SF scaffolds with unique fiber structures, mechanical and biological properties, making them highly promising for regenerative medicine applications.

The Past, Present, and Future of Tubular Melt Electrowritten Constructs to Mimic Small Diameter Blood Vessels – A Stable Process?

“…This behavior is commonly referred to as J-Shape Stress-Strain behavior or nonlinear viscoelastic behavior of stress stiffening. [30,[79][80][81] Replicating this characteristic is a benchmark for synthetic vascular grafts to reduce the mechanical mismatch and allow the grafted tubular structure to better incorporate into the physiological tissue and minimize the risk of inducing a rapid graft occlusion due to blood flow disturbances and the resulting accumulation of platelets at the grafting site. [6,8] Artificial grafts need to replicate Challenges of the field of small diameter vascular grafts.…”