Microstructured silk fiber scaffolds with enhanced stretchability.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Polymer Chemistry

Background:

• Current 3D silk fibroin (SF) scaffold fabrication methods lack control over molecular rearrangement and hierarchical organization, leading to brittle structures.
• Embrittlement in SF scaffolds is often caused by excessive β-sheet nanocrystal formation, hindering their application in tissue engineering.

Purpose of the Study:

• To develop a novel fabrication process for creating 3D silk fibroin scaffolds with controlled molecular structure and hierarchical organization.
• To investigate the mechanical properties, cell compatibility, and extracellular matrix deposition of the fabricated scaffolds.

Main Methods:

• Electrowriting of aqueous silk fibroin solutions followed by post-processing with an aqueous sodium dihydrogen phosphate solution.
• Characterization of scaffold architecture, β-sheet and random coil conformations, mechanical properties, and *in vitro* cell behavior.

Main Results:

• The developed process enabled controlled gelation of SF, balancing β-sheet formation with random coil structures, resulting in stable, compliant scaffolds (0.5-15 MPa modulus).
• The scaffolds exhibited high porosity (~97%) and precise control over microfiber architecture (400 μm inter-fiber distance).
• *In vitro* studies showed excellent human renal epithelial and endothelial cell adherence, proliferation, and organization, with >95% viability and type-IV collagen deposition.

Conclusions:

• This electrowriting and post-processing approach yields stable, organized 3D silk fibroin scaffolds with tunable mechanical and biological properties.
• The fabricated scaffolds demonstrate significant potential for various tissue engineering applications due to their balanced molecular structure and excellent cell integration.