Tissue Engineering Approaches to Modulate the Inflammatory Milieu following Spinal Cord Injury

Tissue engineering strategies have shown promise in promoting healing and regeneration after spinal cord injury (SCI); however, these strategies are limited by inflammation and the immune response. Infiltration of cells of the innate and adaptive immune responses and the inflammation that follows cause secondary damage adjacent to the injury, increased scarring, and a potently inhibitory environment for the regeneration of damaged neurons. While the inflammation that ensues is typically associated with limited regeneration, the immune response is a crucial element in the closing of the blood-brain barrier, minimizing the spread of injury, and initiating healing. This review summarizes the strategies that have been developed to modulate the immune response towards an anti-inflammatory environment that is permissive to the regeneration of neurons, glia, and parenchyma. We focus on the use of biomaterials, biologically active molecules, gene therapy, nanoparticles, and stem cells to modulate the immune response, and illustrate concepts for future therapies. Current clinical treatments for SCI are limited to systemic hypothermia or methylprednisolone, which both act by systemically mitigating the effects of immune response but have marginal efficacy. Herein, we discuss emerging research strategies to further enhance these clinical treatments by directly targeting specific aspects of the immune response.