Beyond Scar Removal: Reprogramming the Glial Scar for Neural Repair

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Abstract
Spinal cord injury (SCI) research has long treated the glial scar as the central obstacle to regeneration. That view is useful, but it is now too narrow. The scar is not a passive wall. It is an evolving repair tissue that contains inflammation, stabilizes the lesion, remodels extracellular matrix, and, under many conditions, restricts axonal growth. The next phase of SCI therapy should therefore move from scar suppression to scar reprogramming. In this Opinion, I argue that the field should prioritize temporally precise, spatially targeted, and biomarker-guided interventions that preserve the protective functions of the scar while reducing its chronic inhibitory features. Cell transplantation, biomaterials, neurotrophic factors, gene therapy, immunomodulation, and neuromodulation each offer important strengths, but none is sufficient as a stand-alone regenerative therapy. The most credible path forward is a staged combinatorial strategy that converts the lesion microenvironment into a permissive, instructive, and trainable tissue bridge.

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