Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Abstract

Spinal cord injury (SCI) disrupts nerve pathways and affects sensory, motor, and autonomic function. There is currently no effective treatment for SCI. SCI occurs within three temporal periods: acute, subacute, and chronic. In each period there are different alterations in the cells, inflammatory factors, and signaling pathways within the spinal cord. Many biomaterials have been investigated in the treatment of SCI, including hydrogels and fiber scaffolds, and some progress has been made in the treatment of SCI using multiple materials. However, there are limitations when using individual biomaterials in SCI treatment, and these limitations can be significantly improved by combining treatments with stem cells. In order to better understand SCI and to investigate new strategies for its treatment, several combination therapies that include materials combined with cells, drugs, cytokines, etc. are summarized in the current review.

Keywords: biomaterial scaffolds; cell transplantation; spinal cord injury; spinal cord repair; stem cell.

Figure 1

Pathophysiologic mechanisms of SCI. Acute phase: exhibits hematoma formation, Wallerian degeneration of distal axons with demyelination reaction, ROS production, inflammation occurs, ionic imbalance, macrophages phagocytose debris, astrocytes migrate toward the center of the lesion and encapsulate the damaged tissues, microglia are also activated and change their morphology, fibroblasts induce fibroblast reaction, and a large number of fibroblasts are deposited around the core of the lesion. Subacute phase: astrocytes form a glial scar and debris is further engulfed. Chronic phase: progressive generation of empty capsule cavities, myelin debris, deposition of GSPGs and scarred astrocytes.

Figure 2

Combinations of cells and capillary scaffolding. SCI creates cavities that impede axonal signaling. Alginate capillary hydrogels have well-aligned channels that propel cell growth in specific directions. When stem cells derived from embryonic cells are implanted into the alginate hydrogel, they occupy the voids and promote axonal regeneration. Stem cells are able to establish synapse-like connections between host axons and neurons formed by the stem cells within the alginate hydrogel channels, thus promoting spinal cord regeneration (Szymoniuk et al., 2022).