Understanding the Role of Fibrotic Scarring in Shaping the Lesion Site and Neural Repair After Spinal Cord Injury.

Following spinal cord injury (SCI), a complex lesion scar forms at the injury site that matures and remodels over weeks, profoundly influencing neural repair and functional recovery. This lesion consists of a fibrotic scar at its core surrounded by an astrocytic scar (or border). While the astrocytic scar has been extensively studied for decades, the fibrotic scar has only recently emerged as a critical player in post-injury pathophysiology. Fibrotic scarring plays a dual role: it contributes to tissue stabilization and limits secondary damage, yet its persistence can pose a barrier that inhibits axonal regeneration and hinders recovery. Despite growing interest, key aspects of fibrotic scar formation and function remain poorly understood. This review synthesizes the current knowledge of fibrotic scarring after SCI, including its temporal progression, cellular composition, molecular mechanisms, and interactions with other cell types at the injury site, and we discuss emerging therapeutic strategies targeting fibrosis. We further highlight critical knowledge gaps and outline future directions to define how fibrotic scarring shapes the injury microenvironment and influences neural repair.