Stem cell-laden rigid-flexible bioscaffold for neural regeneration and functional recovery after spinal cord injury

Spinal cord injury (SCI) remains a major clinical challenge due to limited neural regeneration and complex neuroimmune responses. To address these barriers, this study engineered a rigid-flexible composite bioscaffold (Poly_NT3_gel) integrating a multi-channel conduit made of aligned electrospun polycaprolactone (PCL) nanofibers, neurotrophin-3 (NT3)-encapsulated collagen particles, and a chitosan self-healing hydrogel containing bone marrow-derived mesenchymal stem cells (BMSCs). The multi-channel PCL conduit directed axonal growth, while gradient collagen particles enabled sustained NT3 release. The self-healing hydrogel provided tunable mechanics supporting BMSCs proliferation. In a rat complete SCI model, Poly_NT3_gel reduced lesion volume and fibrosis and improved neural bridging, locomotor function, and urinary recovery. Single-nucleus RNA sequencing highlighted bioscaffold-mediated restoration of transcriptional profile, as well as a microenvironment that suppressed post-injury fibroblast proliferation while modulating immune responses. This work established a multicomponent tissue engineering system that synergized physical, biochemical, and cellular cues to overcome key challenges in SCI repair, offering a promising strategy for neural regeneration and functional recovery after SCI. Spinal cord injury remains a major challenge owing to restricted neural regeneration and complex neuroimmune responses. Here, the authors developed a multifunctional bio scaffold that promotes nerve regeneration, modulates immune responses, and improves recovery after spinal cord injury.