ACS Nano: Bringing new hope to the treatment of spinal cord injury, Tongji University's Cheng Liming team improved the immune microenvironment and remodeled neural circuits through nano-layered double hydroxide

Spinal cord injury (SCI) is one of the most common major injuries of the central nervous system.
It often leads to neuronal death and axonal rupture, accompanied by secondary injuries such as cascade inflammation, forming an inhibitory pathological microenvironment.
Its treatment The difficulty lies in how to improve the immune microenvironment of the injured area, so as to achieve nerve regeneration and functional remodeling.

In recent years, the use of functional biomaterials to improve and rebuild the immune microenvironment has become a promising strategy for spinal cord injury repair.

Recently, the team of Professor Liming Cheng from Tongji Hospital of Tongji University published an online research paper titled Immunomodulatory Layered Double Hydroxide Nanoparticles Enable Neurogenesis by Targeting Transforming Growth Factor-β Receptor 2 in ACS Nano magazine.

Relying on the "Regeneration and Repair of Spinal Cord Injury" Key Laboratory of the Ministry of Education, the research team developed a biodegradable, supported by the National Key Research and Development Program "Research on the Mechanism and Translation of Repairing Spinal Cord Injury by Mobilizing Endogenous Neural Stem Cells" Layered double hydroxide (LDH) nanomaterials that can regulate the typing of immune cells in the injured area and inhibit inflammation.

The nanomaterial can significantly promote neural stem cell (NSCs) migration, neural differentiation, activate L-Ca2+ channels and induce the generation of action potentials.

The LDH loaded with neurotrophic factor NT3 to form a nanocomposite system (LDH-NT3) was transplanted into the injured area of ​​spinal cord injury (SCI) mice.
Newly born BrdU+ endogenous NSCs and functional neurons can be seen in the injured area, which significantly improves the spinal cord injury ( SCI) Behavioral and electrophysiological evaluation of mice.

The LDH material itself has the effect of promoting nerve regeneration, and the repair effect of LDH-NT3 on spinal cord injury (SCI) mice is further improved than that of the LDH group.

Figure 1.
Nanomaterials LDH and LDH-NT3 can effectively restore the motor function of SCI mice.
Using pathway analysis (IPA) screening, 57 genes are intertwined to form protein-protein interactions related to neural precursor cell proliferation and immune dysfunction.
Function (PPI) network diagram, in which transforming growth factor receptor 2 (TGFBR2) is highly related to the biological processes of nerve regeneration and immune regulation, and is a key gene for LDH to promote the repair of spinal cord injury.

Immunofluorescence staining of Nestin and TGFBR2 was performed on the lesion, and the results showed that it was co-expressed in the neonatal nerve area of ​​the LDH and LDH-NT3 transplantation groups.

LDH can induce the polarization of the M2 phenotype of microglia and macrophages by activating TGFBR2, and effectively improve the immune microenvironment.

Figure 2.
Material transplantation improves the immune microenvironment of the injured area and promotes the regeneration of nerve cells.
In summary, the study found that layered double hydroxide (LDH) can construct an immune microenvironment suitable for spinal cord injury (SCI) repair.
It can be loaded with various neurotrophic factors, revealing the membrane receptor target of the material to improve the microenvironment and the key molecular mechanism of promoting nerve regeneration, and provide a new strategy for the treatment of spinal cord injury with biological material immune regulation.

Link to the paper: https://pubs.
acs.
org/doi/pdf/10.
1021/acsnano.
0c08727