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ROS-Responsive Injectable Hydrogel Loaded with SLC7A11-modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc
Tian Gao1,2, Guangyu Xu1,2, Tiancong Ma1,2
1Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, 200040, P. R. China.
Advanced Healthcare Materials
|May 1, 2024
Summary
A novel hydrogel delivers modified mRNA to treat intervertebral disc degeneration (IVDD) by targeting oxidative stress. This innovative approach inhibits ferroptosis in nucleus pulposus cells, offering a potential therapy for low back pain caused by IVDD.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Molecular Therapy
Background:
- Intervertebral disc degeneration (IVDD) is a major cause of low back pain, significantly impacting global economies.
- Oxidative stress is a key factor in IVDD development, yet current treatments remain limited.
- Developing effective strategies to combat IVDD and its associated pain is a critical unmet medical need.
Purpose of the Study:
- To develop an innovative treatment for IVDD by targeting oxidative stress.
- To create an injectable, reactive oxygen species-responsive hydrogel for targeted delivery of modified mRNA.
- To investigate the therapeutic potential of upregulating SLC7A11 expression in degenerated intervertebral discs.
Main Methods:
- Synthesis of an injectable reactive oxygen species-responsive hydrogel (PVA-tsPBA) for modified mRNA (modRNA) encapsulation.
- Loading and selective release of chemically synthesized SLC7A11 modRNA within the hydrogel system.
- Local injection of the hydrogel into degenerated intervertebral discs (IVDs) to upregulate SLC7A11 expression and inhibit ferroptosis in nucleus pulposus cells (NPCs).
Main Results:
- The PVA-tsPBA hydrogel demonstrated cleavage in response to reactive oxygen species, enabling controlled release of SLC7A11 modRNA.
- modRNA release was proportional to the severity of IVDD, indicating targeted delivery.
- Inhibition of ferroptosis in NPCs was observed, leading to amelioration of IVDD.
- The developed system showed potential for treating early-stage IVDD.
Conclusions:
- An innovative PVA-tsPBA hydrogel-encapsulated modRNA system was successfully developed for IVDD treatment.
- This system effectively targets oxidative stress and ferroptosis in degenerated intervertebral discs.
- The findings suggest a promising novel therapeutic strategy for early-stage IVDD and associated low back pain.
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