Researchers at the University of Crete and the Foundation for Research and Technology-Hellas (FORTH/IESL) have reported a one-step strategy for fabricating bioactive 3D hydrogel scaffolds using curcumin as a multifunctional photoinitiator in two-photon polymerization (2PP). Posted as a preprint last month, the study says curcumin serves two roles: it enables high-resolution 3D printing while simultaneously imparting antibacterial properties during fabrication, removing the need for post-print modification.
2PP is widely used for micro-scale scaffold fabrication in tissue engineering. However, its broader adoption in hydrogel systems has been constrained by the lack of photoinitiators that combine high nonlinear absorption efficiency with cytocompatibility. Conventional initiators such as Irgacure 2959 exhibit low two-photon absorption cross sections under near-infrared excitation, requiring higher laser intensities that increase the risk of thermal damage and reduced feature fidelity.
Enhanced nonlinear absorption through GelMA–curcumin interaction
In the reported work, curcumin, a naturally derived polyphenol from turmeric, was incorporated into a 10% (w/v) GelMA formulation. Open-aperture Z-scan measurements showed that the GelMA/curcumin mixture achieved a two-photon absorption cross section of approximately 1500 Goeppert Mayer (GM), compared to roughly 320 GM for curcumin alone.
The researchers attribute this enhancement to interactions between curcumin and hydrophobic amino acid residues in the GelMA backbone. These interactions promote localized aggregation and stronger electronic coupling, increasing nonlinear energy deposition within the focal voxel during printing.
Parametric fabrication studies revealed a broad processing window. The GelMA/curcumin formulation supported polymerization at laser intensities as low as 0.15 TW/cm², with scanning speeds up to 52 mm/s. In comparison, GelMA formulations containing Irgacure 2959, Eosin Y, or Rose Bengal exhibited narrower processing windows and, in some cases, thermal damage at elevated intensities.
Printing complex TPMS and bone-like lattices
Using multiphoton lithography, the team fabricated square lattices, gyroid and Schwarz diamond triply periodic minimal surface (TPMS) architectures, and bone-like lattice structures. Scanning electron microscopy confirmed pore sizes ranging from single-digit microns to over 150 μm, depending on geometry. Optical microscopy of hydrated samples indicated that scaffold architectures remained stable after swelling.
TPMS geometries are widely used in regenerative medicine due to their continuous curvature and high surface-to-volume ratio, which improve nutrient diffusion and cell infiltration.
Stem cell compatibility and dual antibacterial function
Biocompatibility was evaluated using mesenchymal stem cells (MSCs). Although metabolic activity showed an initial reduction on day one, viability recovered to control levels by day three. SEM imaging confirmed cell adhesion, proliferation, and infiltration within the scaffold pores.
Beyond printability and cytocompatibility, the study reports intrinsic antibacterial properties. Under blue LED irradiation (~450 nm), the GelMA/curcumin films achieved approximately 99.9% reduction of Staphylococcus aureus and over 90% reduction of Escherichia coli colony-forming units. A passive antifouling effect was also observed against E. coli, with reduced initial bacterial adhesion compared to GelMA printed with conventional photoinitiators.
The antibacterial effect is attributed to photodynamic generation of reactive oxygen species by curcumin upon light activation. The effect was more pronounced against S. aureus, likely due to differences in bacterial membrane structure that allow greater reactive oxygen species penetration compared to E. coli.
Reframing the role of photoinitiators in biofabrication
In most multiphoton systems, photoinitiators are treated as temporary processing additives. They are either removed post-fabrication or remain chemically inert within the scaffold. This work proposes a different model. By using curcumin as both initiator and bioactive agent, the scaffold gains antimicrobial functionality without secondary coating, drug loading, or surface modification steps.
The study remains at the preprint stage and has not yet undergone peer review. Further work will be required to assess long-term stability, in vivo performance, and scalability beyond micro-scale multiphoton lithography.
Photoinitiator chemistry remains a bottleneck in two-photon biofabrication
2PP research has increasingly focused on improving process reliability and scalability, including efforts to standardize mechanical testing methods for microfabricated structures as the technique moves toward broader biomedical applications. At the same time, recent research demonstrating two-photon polymerization inside living cells has highlighted the precision of the method but also its dependence on tightly controlled photochemical conditions.
Despite continued improvements in hardware resolution and system throughput, progress remains constrained by material formulation. Photoinitiators must balance nonlinear absorption efficiency with cytocompatibility while avoiding thermal damage and competing photochemical pathways. The curcumin-based formulation described in this preprint addresses that constraint by combining photoinitiation and scaffold bioactivity in a single material system.
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Featured image shows electron microscopy image of 3D printed GelMA/curcumin lattice structures. Image via Charitaki et al., 2026 preprint.
