CD44-targeting hyaluronic acid-selenium nanoparticles boost functional recovery following spinal cord injury.

BACKGROUND: Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery. RESULTS: The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI. CONCLUSIONS: These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.

Nanomaterials as therapeutic agents to modulate astrocyte-mediated inflammation in spinal cord injury.

Promoting the recovery of neurological function in patients with traumatic spinal cord injury (TSCI) remains challenging. The balance between astrocyte-mediated neurotrophic and pro-inflammatory responses is critical for TSCI repair. Recently, the utilization of nanomaterials has been considerably explored in immunological reconstructive techniques that specifically target astrocyte-mediated inflammation, yielding positive outcomes. In this review, we aim to condense the present knowledge regarding the astrocyte-mediated inflammation following TSCI. We then review the various categories of nanomaterials utilized in the management of astrocyte-mediated inflammation in TSCI and conclude by summarizing their functions and advantages to offer novel insights for the advancement of effective clinical strategies targeting TSCI.

Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair.

Traumatic spinal cord injury (SCI) can cause severe neurological impairments. Clinically available treatments are quite limited, with unsatisfactory remediation effects. Residing endogenous neural stem/progenitor cells (eNSPCs) tend to differentiate towards astrocytes, leaving only a small fraction towards oligodendrocytes and even fewer towards neurons; this has been suggested as one of the reasons for the failure of autonomous neuronal regeneration. Thus, finding ways to recruit and facilitate the differentiation of eNSPCs towards neurons has been considered a promising strategy for the noninvasive and immune-compatible treatment of SCI. The present manuscript first introduces the responses of eNSPCs after exogenous interventions to boost endogenous neurogenesis in various SCI models. Then, we focus on state-of-art manipulation approaches that enhance the intrinsic neurogenesis capacity and reconstruct the hostile microenvironment, mainly consisting of pharmacological treatments, stem cell-derived exosome administration, gene therapy, functional scaffold implantation, inflammation regulation, and inhibitory element delineation. Facing the extremely complex situation of SCI, combined treatments are also highlighted to provide more clues for future relevant investigations.