Innovative Use of Gallic Acid as a Crosslinking Agent for Gelatin: A Biocompatible Strategy for 3D-Printed Scaffolds in Tissue Engineering.

Gallic acid, a natural phenolic compound, was used as a crosslinking agent to achieve protein-polyphenol conjugation under alkaline conditions, presenting an innovative approach to stabilize gelatin. The formulated inks were evaluated for their rheological properties and 3D printing performance. Once the scaffolds were printed, physicochemical properties were assessed by color changes and FTIR. Additionally, three different post-processing methods were studied to avoid toxicity: incubation in PBS, incubation in NaOH followed by PBS neutralization, and incubation in HCl followed by PBS neutralization. The inks exhibited shear-thinning behavior with self-supporting capacity after extrusion, indicating their suitability for use as inks in 3D printing. After printing, changes in color and in the amide I band/amide II band ratio were observed due to alkaline oxidation, confirming the gelatin crosslinking. Among the tested treatments, incubation in PBS or NaOH followed by neutralizing with PBS proved to be the most suitable for obtaining cytocompatible scaffolds. The mechanical properties demonstrated the suitability of the proposed crosslinking systems for creating scaffolds. This strategy confirms that gallic acid-mediated crosslinking under alkaline conditions enables the fabrication of cytocompatible and mechanically stable gelatin-based scaffolds, making them suitable for tissue engineering.