Synergistic restoration of spinal cord injury through hyaluronic acid conjugated hydrogel-polydopamine nanoparticles combined with human mesenchymal stem cell transplantation

Bioactive Materials, 2025 · DOI: https://doi.org/10.1016/j.bioactmat.2024.09.027 · Published: September 19, 2024

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

Spinal cord injury (SCI) is a devastating condition with limited treatment options because the central nervous system has a restricted ability to regenerate. The accumulation of reactive oxygen species (ROS) and inadequate endogenous neural stem progenitor cells (eNSPCs) in the lesion site exacerbates neurologic deficits and impedes motor function recovery. The study developed a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel. Microglia cells treated with PDA NPs have been shown to reduce intracellular ROS levels by 65 % and suppress the expression of inflammatory cytokines such as IL-1β (decreased by 35 %) and IL-6 (decreased by 23 %), thus mitigating the microglia’s inflammatory response. The H-P-M hydrogel combined with hMSCs transplantation can recruit eNSPCs to the injury site. RNA-seq has unveiled the potential of the H-P-M hydrogel to facilitate eNSPCs neuronal differentiation through the MAPK pathway. Furthermore, these differentiated neurons are integrated into local neural circuits.

Study Duration

8 weeks

Participants

54 female C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
PDA NPs reduce intracellular ROS levels by 65 % and suppress the expression of inflammatory cytokines such as IL-1β (decreased by 35 %) and IL-6 (decreased by 23 %) in microglia cells.
2
The H-P-M hydrogel combined with hMSCs transplantation can recruit eNSPCs to the injury site.
3
H-P-M hydrogel primarily promoted eNSPCs neuronal differentiation through the positive regulation of the MAPK cascade signaling pathway.

Research Summary

This study introduces a novel therapeutic strategy for spinal cord injury (SCI) repair using a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel. The H-P-M hydrogel promotes eNSPCs neuronal differentiation and reduces inflammation. It serves as catalysts inducing 5-HT axon regeneration and improving BMS score after SCI through the modulation of the ROS milieu and the promotion of neuronal differentiation from eNSPCs. The H-P-M hydrogel demonstrates good biocompatibility, degrades within 14 days, shields transplanted MSCs from oxidative damage, increases their survival rate, and reduces pro-inflammatory factors, leading to enhanced motor functional recovery following SCI.

Practical Implications

Improved SCI Treatment

The H-P-M hydrogel offers a promising therapeutic strategy for SCI repair by addressing the limitations of current treatments.

Reduced Inflammation

PDA NPs effectively scavenge intracellular ROS and reduce the level of proinflammatory factors, mitigating the inflammatory response after SCI.

Enhanced Nerve Regeneration

The hydrogel promotes neuronal differentiation of eNSPCs and facilitates the regeneration of 5-HT axons, contributing to motor function recovery.

Study Limitations

1
The study primarily focuses on preclinical animal models.
2
The uncontrolled migration of MSCs may be a weakness in this strategy.
3
Further research is needed to enhance the targeting capabilities of MSCs and enhancing their retention at the injury site.

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