A comprehensive review published in Engineering outlines multi-disciplinary engineering approaches addressing spinal cord injury (SCI), a debilitating central nervous system disorder triggering permanent sensory, motor, and autonomic dysfunction, and imposing heavy burdens on individuals and societies worldwide. The paper, led by researchers from Tianjin Medical University General Hospital and Shandong University, systematically sorts engineering-driven therapeutic pathways and proposes a revised clinical translation framework built on cross-technology integration.

The research team completed systematic literature retrieval across PubMed, ScienceDirect, and Google Scholar covering papers released between 2015 and 2025, ultimately screening 657 qualified studies to unpack the staged pathological progression of traumatic SCI, which accounts for over 90 percent of all SCI cases. The review distinguishes primary mechanical tissue damage from dynamic secondary cascade injuries segmented into acute, subacute, and chronic phases, noting that persistent inflammatory storms, oxidative stress, and late-stage glial-fibrotic scar formation jointly create a microenvironment unfavorable to axonal regeneration, limiting the efficacy of single conventional interventions such as high-dose methylprednisolone and isolated surgical decompression.

The paper elaborates five core engineering therapeutic branches. Neuromodulation technologies cover electrical, ultrasound, magnetic, photobiomodulation, and optogenetic interventions as well as brain–computer interfaces, with epidural spinal cord stimulation emerging as the most widely adopted modality to reactivate dormant spinal circuits and boost motor and autonomic performance in chronic paralyzed patients. Cell therapy summarizes multiple transplantable cell categories including neural stem cells, mesenchymal stromal cells, and olfactory ensheathing cells, and details in-vitro engineering modifications such as genetic editing and preconditioning to improve graft survival and immune regulation capacity. Biomaterials are categorized by structural form into hydrogels, 3D-printed scaffolds, microspheres, nanomaterials, and stimuli-responsive smart substrates, each designed to serve as cell carriers, controlled drug delivery vehicles or directional axonal guidance matrices. The work also summarizes updated surgical techniques and targeted pharmacological and gene interventions that act on inflammatory and regenerative signaling pathways.

The review further dissects prominent translational barriers for each technical category, including low transplanted cell viability, long-term electrode tissue reactivity, insufficient biomaterial mechanical stability, and inconsistent stimulation parameter standards across clinical trials. It highlights the value of multimodal combination regimens, such as pairing biomaterial scaffolds with cell transplantation or coupling neuromodulation with rehabilitation training, to simultaneously target multiple pathological links of SCI. The authors stress that sustained interdisciplinary cooperation across medical and engineering fields is required to standardize evaluation systems, resolve interindividual treatment variability, and streamline the bench-to-bedside research pipeline spanning cell, rodent, non-human primate preclinical models, and tiered human clinical trials. The full text discusses pending ethical and technical hurdles while laying out a progressive developmental roadmap for personalized, combinatorial SCI regenerative therapies.

The paper “Frontier Integration in Spinal Cord Injury Repair: Engineering-Driven Mechanistic Exploration and a New Paradigm for Clinical Translation,” is authored by Mi Zhou, Xue Yao, Boya Huang, Jie Ren, Haiwen Feng, Shiqing Feng. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.11.012. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.