Abstract
The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.
Highlights
The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial
Infiltrating macrophages and in situ activated microglia reached their respective peaks at focal area on 3 and 7 days after injury and polarized into “classically activated macrophage (M1)” due to the effect of tumor necrosis factor (TNF)-α and other proinflammatory factors responsible for the secretion of more proinflammatory factors, which further led to the aggravation of the injury and formation of scar tissue[3,4]
In the study of conventional tissue engineering using biomaterials to transmit biological information to promote neural differentiation of stem cells, nerve repair is at risk of failure under the influence of severe immune inflammation exerted by acute SCI8
Summary
The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. It could be concluded that the constructed nerve fiber membrane was highly responsive to the microenvironment of SCI, and the rapid release of loaded plasmid liposomes played its role in transfection, with the resulting IL-4 inducing the polarization of microglia and macrophages to M2 type in time (Supplementary Fig. 6).
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