Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury

After spinal cord injury (SCI), endogenous neural stem cells (NSCs) near the damaged site are activated, but few NSCs migrate to the injury epicenter and differentiate into neurons because of the harsh microenvironment. It has demonstrated that implantation of hydrogel scaffold loaded with multiple cues can enhance the function of endogenous NSCs. However, programming different cues on request remains a great challenge. Herein, a time-programmed linear hierarchical structure scaffold is developed for spinal cord injury recovery. The scaffold is obtained through coaxial 3D printing by encapsulating a dual-network hydrogel (composed of hyaluronic acid derivatives and N-cadherin modified sodium alginate, inner layer) into a temperature responsive gelatin/cellulose nanofiber hydrogel (Gel/CNF, outer layer). The reactive species scavenger, metalloporphyrin, loaded in the outer layer is released rapidly by the degradation of Gel/CNF, inhibiting the initial oxidative stress at lesion site to protect endogenous NSCs; while the inner hydrogel with appropriate mechanical support, linear topology structure and bioactive cues facilitates the migration and neuronal differentiation of NSCs at the later stage of SCI treatment, thereby promoting motor functional restorations in SCI rats. This study offers an innovative strategy for fabrication of multifunctional nerve regeneration scaffold, which has potential for clinical treatment of SCI.