Vitamin C-Induced Photo-Redox Threshold Enables High-Fidelity Volumetric Printing of Collagen.

Tomographic volumetric printing (TVP) enables rapid fabrication of complex, centimeter-scale 3D architectures. TVP of native proteins such as collagen is attractive because it preserves native bioactive motifs that regulate cell-matrix signaling. However, direct TVP of collagen remains challenging because dityrosine crosslinking, driven by visible-light-activated Ru(II)bpy3 2+/sodium persulfate (SPS), lacks an effective inhibitory mechanism. This results in near-immediate crosslinking upon light exposure, leading to an insufficient nonlinear threshold response that fails to suppress background curing. Here, we introduce vitamin C (L-ascorbic acid) as a biocompatible redox regulator to overcome this limitation. We demonstrated that vitamin C established a photo-redox threshold by suppressing Ru(III) accumulation and scavenging persulfate radicals within the Ru/SPS system, thereby delaying dityrosine crosslinking until vitamin C depletion. This threshold generated the nonlinear response required for TVP, enabling high-fidelity volumetric printing of collagen. Post-printing construct densification (∼53% shrinkage) further improved feature resolution (80 µm positive; 120 µm negative) and yielded mechanically stable and highly stretchable hydrogels (up to 180% strain). Collagen resin with vitamin C supported both cell seeding post-printing and cell-laden printing with high cell density and viability, enabling the rapid biofabrication of cell-instructive 3D microenvironments.