Magnesium Oxide/Poly(l-lactide-co-𝝐-caprolactone) Scaﬀolds Loaded with Neural Morphogens Promote Spinal Cord Repair through Targeting the Calcium Inﬂux and Neuronal Diﬀerentiation of Neural Stem Cells

Advanced Healthcare Materials, 2022 · DOI: 10.1002/adhm.202200386 · Published: June 3, 2022

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study addresses the limited regenerative ability of the central nervous system after spinal cord injury (SCI) by developing a novel biomaterial scaffold. The scaffold is made of magnesium oxide (MgO) and poly (l-lactide-co-ε-caprolactone) (PLCL) and loaded with purmorphamine (PUR) and retinoic acid (RA) to promote spinal cord repair. The implanted scaffold releases magnesium ions to reduce cell death and delivers PUR/RA to encourage neural stem cells to become neurons, leading to improved motor function recovery in SCI mice.

Study Duration

8 weeks

Participants

ICR female mice (25 g ± 5 g)

Evidence Level

In vivo animal study and In vitro experiments

Key Findings

1
The MgO/PLCL scaffold releases magnesium ions that attenuate cell apoptosis by blocking calcium influx in the injured spinal cord.
2
The PUR/RA loaded in the scaffold promotes the recruitment and neuronal differentiation of endogenous neural stem cells (NSCs) at the SCI lesion site.
3
The PUR/RA-loaded MgO/PLCL scaffold facilitates partial recovery of locomotor function in SCI mice, suggesting it as a promising biomaterial for clinical treatment.

Research Summary

The study introduces a PUR/RA-loaded MgO/PLCL scaffold designed to address the challenges of spinal cord injury (SCI) treatment. In vitro results demonstrate that the MgO component provides neuroprotection by neutralizing the acidic environment and reducing NMDA-induced apoptosis. In vivo experiments show that the scaffold promotes recruitment and differentiation of NSCs, reduces glial scar formation, and facilitates partial recovery of locomotor function in SCI mice.

Practical Implications

Clinical Translation

The PUR/RA-loaded MgO/PLCL scaffold shows promise as a potential biomaterial for clinical treatment of SCI due to its ability to promote nerve regeneration and functional recovery.

Biomaterial Design

The study highlights the importance of incorporating neuroprotective agents (MgO) and neural morphogens (PUR/RA) into biomaterial scaffolds for effective SCI repair.

Targeted Therapy

The scaffold provides a targeted approach to SCI treatment by addressing multiple pathological factors, including calcium influx, glial scar formation, and neuronal differentiation.

Study Limitations

1
The study is limited to a mouse model of SCI, and further research is needed to validate the findings in larger animal models or human clinical trials.
2
The long-term effects and potential complications of MgO degradation and Mg2+ release in vivo require further investigation.
3
The specific mechanisms underlying the interaction between the scaffold and endogenous NSCs need to be further elucidated.

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