One-Step Fabrication and Biofunctionalization of 3D GelMA-based Scaffolds through GelMA-Curcumin Co-Initiated Two-Photon Polymerization

Two-photon polymerization (2PP) enables the fabrication of complex 3D scaffolds for tissue engineering, yet the lack of biocompatible and bioactive photoinitiators remains a bottleneck for functional bio-manufacturing. Here, a one-step strategy is presented using curcumin (CUR), a naturally derived polyphenol, as a high-efficiency multifunctional photoinitiator for gelatin methacryloyl (GelMA) hydrogels. Nonlinear optical characterization reveals a synergistic interaction between CUR and the GelMA protein backbone, resulting in a significantly enhanced two-photon absorption cross-section (σ ≈ 1500 GM) that outperforms conventional initiators. This synergy facilitates an exceptionally broad processing window and high-speed fabrication (up to 52 mm/s) of high-fidelity, complex triply periodic minimal surface (TPMS) and biomimetic bone-like scaffolds. Beyond its initiation efficiency, CUR imparts intrinsic multifunctionality to the resulting 3D constructs. The scaffolds exhibit exceptional biocompatibility with mesenchymal stem cells while demonstrating a potent dual-action antimicrobial defense: a selective passive antifouling effect against E. coli and active photodynamic eradication (>99.9%) of S. aureus upon blue LED irradiation. This "all-in-one" approach transforms the photoinitiator from an inert processing tool into a source of intrinsic scaffold bioactivity, eliminating the need for complex post-fabrication functionalization.