Severe spinal cord injury (SCI) induces massive proliferation of spinal cord neural stem cells (NSCs), which are considered a promising cell source for therapeutic neural repair. However, most injury-activated spinal cord NSCs differentiate into astrocytes, rather than neurons, in the lesion site as a result of the injury-derived microenvironment. In this mini-review, we introduce the concept of tuning injury-activated endogenous NSCs by implantation of functionalized collagen scaffolds for severe SCI repair. The current state of in situ modulation of migration, scar formation, neuronal differentiation, and functional integration of injury-activated NSCs and their progeny by implantation of elaborately modified collagen scaffolds is demonstrated. Moreover, challenges and perspectives for utilizing injury-activated NSCs for regenerative repair of severe SCI are also discussed.