Silk fibroin–reinforced bioink for high-fidelity 3D printing and tissue regeneration

Digital light processing (DLP) 3D printing is a technology for additive fabrication of objects layer by layer, guided by digital 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. Herein, we introduce silk fibroin (SF) into the conventional PEGDA/CSMA bioink to enhance the precision of DLP 3D printing. The incorporation of SF achieves 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 366.1% 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 induces SF β-sheet structure formation and reduces 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 possesses antibacterial potential, inhibiting E. coli by about 41.3% and S. aureus by about 45.8% within 12 h in vitro. The porous scaffolds are printed with a designed PEGDA/CSMA/SF bioink and effectively accelerate defect repair in rat full-thickness skin wound models (about 19.1% of the untreated control group). Histological analysis reveals that the PEGDA/CSMA/SF hydrogel scaffold promotes angiogenesis and collagen deposition, upregulates VEGFA expression, and downregulates TNF-α expression. The straightforward approach of introducing SF into traditional bioinks represents a promising strategy for DLP 3D printing in tissue regeneration.