Silk fibroin-reinforced bioink for high-fidelity 3D printing and tissue regeneration
Digital light processing (DLP) three-dimensional (3D) printing is an additive manufacturing technique that fabricates objects layer by layer using digitally projected light patterns. It effectively addresses the demand for complex geometries and is widely adopted in the biological field. However, traditional macromolecular bioinks still suffer from printing inaccuracies due to light scattering and runaway free-radical reactions. In this study, we introduced silk fibroin (SF) into the conventional poly(ethylene glycol) diacrylate (PEGDA)/chitosan methacrylate (CSMA) bioink to enhance the precision of DLP 3D printing. The incorporation of SF achieved a significant improvement in mechanical property (alcohol-induced β-sheet formation increased the compressive modulus from 9.5 kPa to 208.1 kPa) and anti-swelling performance (volume swelling ratio from about 366.5% to 144.6%) of cell-free PEGDA/CSMA/SF hydrogel via alcohol treatment, meeting the enhanced mechanical requirements and addressing the commonly neglected issue of geometric deformation of 3D-printed hydrogels caused by swelling in moist environments. Ethanol treatment induced SF β-sheet structure formation and reduced PEGDA/CSMA/SF hydrogel pore size (from about 78.3 μm to 23.6 μm), thereby enhancing the hydrogel network crosslinking. The PEGDA/CSMA/SF bioink exhibited antibacterial potential, inhibiting Escherichia coli by about 41.3% and Staphylococcus aureus by about 45.8% within 12 h in vitro. The porous scaffolds were printed with a designed PEGDA/CSMA/SF bioink and effectively accelerated defect repair in rat full-thickness skin wound models (about 19.1% of the untreated control group). Histological analysis revealed that the PEGDA/CSMA/SF hydrogel scaffold promoted angiogenesis and collagen deposition, upregulated vascular endothelial growth factor A expression, and downregulated tumor necrosis factor-α expression. The straightforward approach of introducing SF into traditional bioinks represents a promising strategy for DLP 3D printing in tissue regeneration.

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