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Riboflavin-5′-phosphate mediated blue-light photocrosslinking of poly(α-amino acid) bioinks for 3D bioprinting applications

2026/03/05 by Ana Elena Morán Espinoza, Jana Dvořáková, Anna Golunova +3 · 1 voice
Engineering · Neuroscience · #3D Printing in Biomedical Research #Electrowetting and Microfluidic Technologies #Neuroscience and Neural Engineering

paper · doi:10.1016/j.reactfunctpolym.2026.106710

openalex publication_date 2026/03/05 · openalex created_date 2026/03/06 · openalex updated_date 2026/04/09

Abstract

3D bioprinting requires biocompatible and rheologically tuned bioinks. In this study, we present the initial use of a visible-light riboflavin-5′-phosphate (FMN)/L-arginine photoinitiation system with synthetic, fully degradable poly(α,L-amino acid) (PolyAA) precursors, specifically methacrylated poly( N 5 –2-hydroxyethyl- l -glutamine) (PHEG-MA) and hyaluronic acid methacrylated (HA-MA). Systematic evaluation of FMN (0.1–0.5% w / v ) and L-arginine (1–2% w/v) concentrations revealed a specific kinetic window for efficient gelation under mild visible light (450 nm, 30 mW/cm 2 ). The resulting PHEG-MA and HA-MA hydrogels exhibited high yield and tunable cross-linking density and mechanical properties.These findings led us to develop a range of bioinks made from PHEG-MA for 3D bioprinting. To address the low inherent viscosity of PHEG-MA, we developed a modular bioink platform using HA-MA and guar gum as rheological modifiers. This approach enabled high-fidelity fabrication across multiple 3D bioprinting setups, including temperature-controlled extrusion, electromagnetic droplet (EMD) and photocuring printheads on a the Cellink BIO X 3D printer. The resulting constructs exhibited structural stability in culture and maintained high viability of encapsulated HEK 293 T cells, establishing these modular PolyAA-based formulations as a versatile, cell-friendly, and synthetic alternative to animal-derived bioinks, such as gelatin methacrylate (GelMA). This demonstated theirpotential for use in tissue engineering applications. • This is the first implementation of visible-light FMN/L-arginine photoinitiation for the synthesis of fully degradable poly(α-amino acid) (PolyAA) precursors. • Optimized FMN:L-arginine ratios (1:10) overcome radical quenching and define precise kinetic windows for PolyAA gelation. • Modular rheological tuning using HA-MA and guar allows for precise electromagnetic droplet (EMD) and extrusion-based bioprinting. • Visible-light curing preserves high cell viability, providing a synthetic, animal-free alternative to GelMA bioinks.

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