New hope for treating intervertebral disc degeneration with engineered vesicles

Intervertebral Disc Degeneration (IVDD) is a painful condition affecting many people, often worsened by excessive exercise. Researchers are exploring innovative treatments to repair the damage caused by IVDD. A recent study highlights the potential of using engineered extracellular vesicles (EVs) in combination with a new delivery system to provide an effective treatment for IVDD.

Understanding IVDD and the Role of Exercise

IVDD occurs when the discs between the vertebrae in our spine start to break down, causing pain and reduced mobility. One factor contributing to IVDD is excessive exercise, which can stress and damage the discs. The nucleus pulposus (NP) cells in these discs play a crucial role in maintaining disc health. When these cells become senescent (aging and no longer functioning properly), they contribute to IVDD.

The Innovation: Engineered EVs and Microneedle Assay

To address this problem, researchers at the Huazhong University of Science and Technology have developed a novel treatment approach using engineered EVs. EVs are tiny particles released by cells that can carry proteins and other molecules to target cells. These engineered EVs are designed to deliver specific therapeutic proteins to the NP cells in the spine.

The researchers created a special microneedle (MN) assay that releases these engineered EVs sustainably. This system is powered by a triboelectric nanogenerator (TENG), which harvests mechanical energy from exercise. When activated by exercise, the TENG triggers the release of the EVs directly into the damaged discs.

Self-powered triboelectric-responsive MNs with
controllable release of EXPLOR engineered EV for IVDD repair

Fig. 1

A Self-powered triboelectric-responsive EXPLOR engineered EV release for biologically targeted IVDD treatment via optically reversible protein-protein interactions. B EXPLOR engineered EV-delivered TRAM1 protein increased TRAM1-TREX1 complex assembly, blocking TREX1 nuclear localization and promoting TREX1 anchoring in the ER, which exhibited protective effects for cytosolic damaged DNA elimination, inhibited cGAS-STING axis activation-mediated inflammatory response and alleviated the progression of IVDD. C Schematic of EXPLOR engineered EV loading and release of triboelectric-responsive MNs using the electrochemical characteristics of polypyrrole (PPy). Polytetrafluoroethylene (PTFE) and indium tin oxide-polyester (ITO-PET) acted as two dissimilar frictional layers. Polylactic acid (PLA) and the Aurum (Au) layer acted as triboelectric-responsive MNs for controllable release of EXPLOR engineered EVs. D Wearable self-powered triboelectric-responsive MNs for controllable release of EXPLOR engineered EVs. E Electrical output under various motion frequencies ranging from 0.5 to 2.5 Hz, including Voc, Isc, and Qtr (Representative plot of three independent technical experiments).

How Does It Work?

  1. Exercise and Inflammation: Excessive exercise can cause NP cells to sense cytosolic DNA, leading to inflammation and accelerating IVDD.
  2. TRAM1 and TREX1 Proteins: TREX1 is a nuclease protein that helps maintain DNA integrity in cells. In senescent NP cells, the disassembly of the TRAM1-TREX1 complex disrupts TREX1’s function, leading to DNA damage.
  3. Engineered EVs: The researchers engineered EVs to carry TRAM1 protein, which helps restore TREX1 function. These EVs are delivered to the NP cells to repair the damage and reduce inflammation.
  4. TENG Activation: The TENG device uses the mechanical energy from exercise to control the release of these engineered EVs, ensuring they are delivered precisely when needed.

Promising Results and Clinical Potential

This innovative approach shows great promise for treating IVDD. The engineered EVs effectively target and repair senescent NP cells, potentially reversing the damage and improving disc health. The controlled release mechanism ensures that the treatment is both timely and efficient.

Conclusion

The combination of engineered EVs and a self-powered microneedle delivery system represents a significant advancement in treating IVDD. By harnessing the body’s mechanical energy from exercise, this approach provides a targeted and sustainable treatment option. This research paves the way for new therapies that could greatly improve the lives of those suffering from IVDD and other degeneration-related disorders.

Zhang W, Qin X, Li G et al. (2024) Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair. Nat Commun [Epub ahead of print]. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *

*