3D-Printed Cellulose Aerogels Minimally Cross-Linked with Polyurea: A Robust Strategy for Tissue Engineering

Cellulose and its derivatives are increasingly explored in biomedical applications due to their biocompatibility, biodegradability, and mechanical performance. In regenerative medicine, aerogel scaffolds with tunable morphology and composition are highly valued for their ability to support tissue regeneration. Three-dimensional (3D) printing offers an effective method to fabricate aerogels with hierarchical pore structures, comprising interconnected macropores and mesopores, that are crucial for tissue engineering. For clinical use, 3D printing should ensure the structural integrity of printed structures and achieve a printing resolution that allows for customization. In this work, the X-aerogel technology, implemented via polyurea cross-linking, was applied to 3D-printed cellulose structures, thereby expanding the potential applications of both technologies. Specifically, 3D-printed methylcellulose (MC) and MC doped with bacterial cellulose nanofiber (MCBCf) gels were cross-linked with an aliphatic polyurea, yielding, after supercritical drying, the corresponding (X-MC and X-MCBCf) aerogels. Elaborate characterization with ATR-FTIR, XPS, ToF-SIMS, N₂ porosimetry, He pycnometry, and SEM confirmed the formation of polyurea on the biopolymer framework, reinforcing the structure and improving the mechanical properties without altering the morphology or textural characteristics of the materials. A significant outcome of cross-linking with polyurea is the long-term stability of X-MC and X-MCBCf aerogels in water, in contrast to their native counterparts, and their capacity to absorb water up to 1800% w/w within only 2 h. Preliminary biological evaluation of the materials, including in vitro (cell compatibility, hemolytic activity), in ovo (HET-CAM), and in vivo (A. salina model) tests, showed good cell viability, blood compatibility, and safety for living organisms. From a fundamental materials perspective, the most important finding of this work is the disproportionally high stability of X-MC and X-MCBCf in physiological environments, achieved with only a minimal (almost undetectable) amount of cross-linking polyurea. From an application standpoint, the findings of this study, collectively, position these aerogels as sustainable and promising candidates for tissue engineering scaffolds.