3D-Printed, Cellulose-Derived Scaffold Promotes Neuroregeneration and Functional Recovery after Spinal Cord Injury

Spinal cord injury (SCI) poses a serious threat to human health. Addressing this condition presents major challenges, primarily in reducing neurotoxicity and promoting nerve regeneration. Here, we developed an innovative three-dimensional (3D) cellulose scaffold with hierarchically ordered multiscale channels, specifically designed to facilitate spinal cord repair. This bioinspired architecture is crucial, as it not only provides a physical guide for axonal growth but also supports cellular adhesion, proliferation, and differentiation. We identified that the scaffold's regenerative efficacy is critically dependent on its filling degree within the lesion cavity, a finding that underscores the pivotal role of precise structural modulation in achieving functional recovery. Beyond providing structural support, this scaffold actively interacts with the hostile injury milieu. It positively regulates the post-SCI immune microenvironment by modulating inflammatory responses, which in turn enhances robust cellular infiltration, facilitates directional axonal growth, and encourages neuronal differentiation. We conclusively demonstrated its significant therapeutic potential for spinal cord regeneration in a mouse model of spinal cord injury, observing marked functional improvements and histological evidence of repair. The core innovation of this 3D platform lies in its versatility; by systematically adjusting scaffold structural parameters such as channel size and porosity, we can strategically optimize the injury-site microenvironment. 3D scaffolds with an 80% filling degree exhibit favorable structure and excellent regulatory properties, effectively facilitating the repair of SCI. This tunable system offers a promising and versatile solution for spinal cord repair, effectively bridging a critical gap in current treatments and paving the way for new regenerative therapeutic strategies.