Researchers from Tongji Hospital’s Department of Orthopedics at Tongji University in Shanghai have been using a nanobiomaterial called layered double hydroxide (LDH) to block the inflammatory environment surrounding spinal cord injuries in mice, acceleration of neurons regeneration and reconstruction of the neural circuit in the spine.
The researchers were also able to identify the underlying genetic mechanism by which LDH works. This understanding should further modify the treatment that may, in conjunction with other elements, result in an appropriate complementary system for the relief of spinal injuries in humans.
The research appears in the journal Chemical Society of America ACS Nano on 2 February.
There is no effective treatment for spinal injuries, which are always accompanied by death of neurons, rupture of axons, or nerve fibers, and inflammation.
Even though new neural stem cells are still being generated by the body, this inflammatory microenvironment (the immediate small conditions at the site of the injury) severely inhibits the regeneration of neurons and axons. Worse still, prolonged activation of immune cells in this area also leads to secondary lesions of the nervous system, which in turn prevents the stems from differentiating into new cell types. .
If this aggressive immune response at the site of the injury could be modeled, there is a possibility that neural stem cells may begin to differentiate and that neural regeneration may occur.
Image title: Nanobiomaterial stimulates neuronal growth in mice
Caption image: Researchers from Tongji Hospital Orthopedics Department have been using a nanobiomaterial called double-layered hydroxide (LDH) to block the inflammatory environment surrounding spinal injuries in mice, accelerating relapse -reovation of neurons and reconstruction of the neural circuit in the spine.
Image credit: Liming Cheng, Rongrong Zhu, Department of Orthopedics, Tongji Hospital Tongji University
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In the last few years, a number of modern nano-scale biomaterials – natural or synthetic materials that interact with biological systems – have been designed to aid in the activation of cloud cells, along with the movement and the difference. Some of these “nanocomposites” are capable of delivering drugs to the injury site and accelerating neuronal regeneration.
These nanocomposites are particularly attractive for spinal manipulation due to their low potency. However, few have the ability to inhibit or moderate the immune response at the site, so do not address the underlying problem. Moreover, the basic methods of how they work are not clear.
Nanolayered double hydroxide (LDH) is a type of clay with many interesting biological properties associated with spinal cord injury, including good biocompatibility (ability to avoid rejection by the body), bio -safe evaluation (breakdown and removal of the molecules after application), and excellent. anti-inflammatory ability. LDH has already been extensively studied in biochemical engineering in terms of immune response management, but mainly in the field of anti-tumor therapy.
These properties made LDH very promising for the creation of a much more beneficial microclimate for overcoming spinal injuries.. “
Rongrong Zhu, First Author Study, Department of Orthopedics, Tongji Hospital Tongji University
Under the direction of Liming Cheng, the corresponding author of the study, the research team injected the LDH into the site of a mouse injury, and found that the nanobiomaterial had signified neural, neural cell gas migration di? Erentiation, activation of channels for neuron excitation, and induction of nerve impulse function. The mice were also found to enjoy much better locomotive behavior compared to the control group of mice.
Furthermore, when the LDH was combined with Neurotrophin-3 (NT3), a protein that stimulates the growth and differentiation of new neurons, the mice had even better regenerative effects than the LDH alone. In fact, the NT3 stimulates neuronal development while the LDH creates an environment where that development is allowed to thrive.
Then, through transcriptional profiling, or gene expression analysis of thousands of genes simultaneously, the researchers were able to help identify how the LDH is performing. They found that once LDH binds to organ organs, it stimulates increased activation of the “growth receptor β 2” (TGFBR2) gene, reducing white blood cell production which increases inflammation and increases the production of white blood cells that inhibit inflammation. When a chemical inhibiting TGFBR2 was applied, they found that the beneficial effects were reversed.
Understanding how LDH achieves these effects should now allow the researchers to tweak the treatment to improve its performance and ultimately create a complete therapeutic system for spinal injuries – combining of these biomaterials with neurotrophic factors such as NT3 — which can be used in clinically applied humans.
Department of Orthopedics, Tongji Hospital Tongji University
Zhu, R., et al. (2021) Immunomodulatory Layered Hydroxide Dual Nanoparticles Enable Neurogenesis by Focusing on Growth β-receptor Transformation 2. ACS Nano. doi.org/10.1021/acsnano.0c08727.