Abstract: The fibrotic scar due to excessive deposition of extracellular matrix (ECM) after spinal cord injury (SCI) remains one of formidable challenges to axonal regeneration. Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking (Göritz et al., 2011) or inhibiting (Dias et al., 2018) the generation of scar-forming stromal cells, as well as inducing their migratory defect (Hellal et al., 2011; Ruschel et al., 2015). Although these approaches help reduce fibrotic scarring, it is insufficient to fully reverse the pathological consequences of fibrosis. Increasing evidence shows that fibrotic scars actually play important positive roles by sealing the lesion and preserving tissue integrity. Moreover, interactions between regenerating axons and ECM are indispensable for axonal elongation and growth (Anderson et al., 2018). This dual nature of healthy physiological ECM and pathological scars means that eliminating the fibrotic scar is not ideal for SCI repair.