Acetylated glucomannan-CNT scaffolds with dual-drug release promote hiPSCs-driven cortical regeneration by suppressing inflammation and anoikis.

The regenerative capacity of the central nervous system is extremely limited, posing significant challenges for repairing brain injuries. Human induced pluripotent stem cells (hiPSCs) offer a promising cell source for neural regeneration, but their clinical application is hindered by inefficient neuronal differentiation, and poor post-transplant survival. To overcome these challenges, we prepared electrospun fibrous membranes composed of acetylated glucomannan, gelatin, polycaprolactone, and carbon nanotubes. These scaffolds exhibited anti-inflammatory properties in vitro and in vivo. Their excellent adhesion and support properties mimic the extracellular matrix, facilitating the 3D culture of our previous engineered NILB-hiPSCs in vitro. After loading with doxycycline (differentiation inducer) and cyclosporin A (immunosuppressant), the scaffolds achieved sustained release of these agents, ensuring timely neuronal differentiation and maintaining localized immunosuppression, thereby circumventing the need for high systemic doses. Moreover, the composites improved the survival and differentiation of NILB-hiPSCs, promoting the neural repairment in controlled cortex injury mice. Our study highlights the importance of customized multifunctional biomaterials in stem cell transplantation therapy.