Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury

Tissue engineering provides a path forward for emerging personalized medicine therapies as well as the ability to bring about cures for diseases or chronic injuries. Traumatic spinal cord injuries (SCIs) are an example of a chronic injury in which no cure or complete functional recovery treatment has been developed. In part, this has been due to the complex and interconnected nature of the central nervous system (CNS), the cellular makeup, its extracellular matrix (ECM), and the injury site pathophysiology. One way to combat the complex nature of an SCI has been to create functional tissue-engineered scaffolds that replace or replenish the aspects of the CNS and tissue/ECM that are damaged following the immediate injury and subsequent immune response. This can be achieved by employing the tissue-engineering triad consisting of cells, biomaterial(s), and environmental factors. Stem cells, with their innate ability to proliferate and differentiate, are a common choice for cellular therapies. Natural or synthetic biomaterials that have tunable characteristics are normally used as the scaffold base. Environmental factors can range from drugs to growth factors (GFs) or proteins, depending on if the idea would be to stimulate exogeneous or endogenous cell populations or just simply retain cells on the scaffold for effective transplantation. For functional regeneration and integration for SCI, the scaffold must promote neuroprotection and neuroplasticity. Tissue-engineering strategies have shown benefits including neuronal differentiation, axonal regeneration, axonal outgrowth, integration into the native spinal cord, and partial functional recovery. Overall, this review focuses on the background that causes SCI to be so difficult to treat, the individual components of the tissue-engineering triad, and how combinatorial scaffolds can be beneficial toward the prospects of future SCI recovery. Impact Statement Traumatic spinal cord injuries (SCIs) change a patient's life instantaneously and have no long-term therapeutic treatment to reverse damage and provide functional neurological recovery. The challenge with SCIs is the irreversible damage immediately done along with secondary injuries that can develop months to years following the initial injury. The tissue-engineering triad consisting of cells, biomaterial(s), and environmental factors has the potential to provide the base for promoting neuroprotection and neuroplasticity and reconnecting the injured area with the noninjured spinal cord. Reviewing current trends in research can help inform the best path forward to create efficacious tissue-engineering scaffolds for SCI regeneration and recovery.