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

Abstract

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.

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

“…This difference was not significant. IL-10 has been extensively revered as an anti-inflammatory cytokine capable of shifting the phenotype of macrophages 22,[44][45][46][47][48] and these studies support the previous findings.…”

Aligned hydrogel tubes guide regeneration following spinal cord injury

“…Given the inflammatory response that occurs after spinal cord injury, we evaluated immune cell infiltration for the distinct material platforms. The spinal cord is immune privileged, but following injury it mounts a robust inflammatory response that leads to further damage and inflammation [68,69]. Immune cell infiltration is necessary after spinal cord injury in order to clear debris, as studies in which immune cells have been depleted result in worse regenerative and functional outcomes [70,71].…”

Combinatorial tissue engineering partially restores function after spinal cord injury

“…Combinatorial strategies to reduce scarring have included methylprednisolone (Chen et al, ; Chvatal et al, ) and chondroitinase ABC to degrade CSPGs (Fouad et al, ; Hwang et al, ; Morice et al, ). Biomaterials that incorporate nanotopographies including pores and nanofibers, the elution of bioactive molecules from nanoparticles and viral gene therapies have also been broadly employed as strategies to reduced fibrosis and gliosis and to alter the profile of recruited macrophages or adaptive T‐cell responses (Dumont, Margul, & Shea, ) following SCI. Combination strategies that influence the interrelationship between the immune response and the developing vasculature has recently been expertly reviewed (Haggerty, Maldonado‐Lasunción, & Oudega, ).…”