CRISPR Precision Meets Self-Powered Bioelectronics in Spinal Cord Recovery: Design Principles, Safety and Regulatory Pathways

Spinal cord regeneration requires a transformative strategy capable of rewriting inhibitory genetic programs while orchestrating real-time electrical communication with regenerating neural tissues. Recent advancements in precision CRISPR genome editing effectively silence or activate crucial molecular gatekeepers such as PTEN, SOCS3, and various epigenetic repressors, thereby reactivating dormant intrinsic regenerative pathways and enabling robust axonal growth. Concurrently, cutting-edge bioelectronic technologies utilizing piezoelectric, triboelectric, and magnetoelectric scaffolds have emerged, adeptly harnessing the body's inherent biomechanical energy. These innovative materials convert subtle physiological micromotions into finely tuned electrical stimuli, precisely guiding neuronal regeneration without external power sources, addressing limitations associated with traditional implants such as infection risks and mechanical incompatibility.Integrating these genetic modifications with bioelectric innovations creates a potent synergy. Genome-level reprogramming amplifies neuronal responsiveness to bioelectrical signals, markedly enhancing axonal regeneration. Simultaneously, autonomous electrical stimulation sustains and stabilizes cellular, metabolic, and synaptic improvements induced by genomic interventions, forming a closed-loop, self-sustaining therapeutic platform. This advanced system significantly transcends conventional transient recovery approaches, moving toward durable, personalized outcomes. Such convergence of advanced genetic engineering and intelligent biomaterial design represents a groundbreaking shift in regenerative neurology.Despite promising preclinical outcomes, significant translational challenges remain. Critical hurdles include ensuring precise delivery of CRISPR tools, mitigating off-target genomic effects, enhancing biocompatibility and scaffold stability, and navigating rigorous regulatory pathways. Addressing these challenges necessitates integrating next-generation gene-editing technologies, comprehensive genomic surveillance, advanced biomaterial sciences, and meticulous preclinical evaluations. Future directions in spinal cord injury research encompass multiplex genome editing, AI-driven scaffold optimization via digital twins, and tailored immune-evasive biomaterials. Collectively, this innovative approach has the potential to redefine regenerative medicine's boundaries, offering unprecedented hope for sustained, personalized recovery and dramatically improving quality of life for individuals affected by spinal cord injuries.