Xeno-Free Biocompatible Peptide-Based Bioinks Reinforced with Cellulose Nanofibers for 3D Printing

Tissue regeneration is a complex biological process with limited self-repair capacity, necessitating engineered solutions to restore both mechanical integrity and biological functionality. In tissue engineering and regenerative medicine, 3D printing has emerged as a promising tool for fabricating scaffolds that mimic the natural extracellular matrix (ECM). However, many bioinks are derived from animal sources, posing risks of pathogen contamination and immune responses. Additionally, many bioinks require chemical cross-linking to achieve mechanical stability, which can leave toxic residues and compromise cell viability. To address these challenges, a fully xeno-free and mechanically stable bioink is developed based on self-assembled peptides and cellulose nanofibers. The bioink combines 9-Fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and its ethylene glycol-conjugated derivative with a biodegradable fibrillar network of cellulose nanofibers, forming a non-cross-linked 3D scaffold. This formulation closely mimics the ECM, as confirmed by high-resolution microscopy, and supports over 95% cell viability, demonstrating exceptional biocompatibility. This work presents a novel xeno-free bioink with self-assembly and self-supporting properties, enabling reproducible 3D printing for advanced biomedical applications, including bone regeneration and personalized medicine.