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A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
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Microenvironment Remodeling Microgel Repairs Degenerated Intervertebral Disc via Programmed Delivery of MicroRNA-155
Chuan Guo1, Yuheng Liu1, Fei Ma1
1Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
ACS Applied Materials & Interfaces
|January 13, 2025
Summary
This study developed a pH-responsive microgel to combat intervertebral disc degeneration (IVDD). The microgel captures lactic acid, reduces inflammation, and prevents cell death, promoting tissue regeneration.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cell Biology
Background:
- Intervertebral disc degeneration (IVDD) involves inflammation, cell apoptosis, and reduced extracellular matrix (ECM) production.
- An acidic microenvironment exacerbates IVDD by promoting inflammation and cell death.
- Targeting pH and apoptosis is crucial for effective intervertebral disc (IVD) regeneration.
Purpose of the Study:
- To design a lactic acid-capturing microgel system for IVD regeneration.
- To develop a pH-responsive delivery vehicle for miRNA-155 and SS31.
- To investigate the therapeutic potential of modulating the acidic inflammatory microenvironment and NPC apoptosis.
Main Methods:
- Fabrication of a chitosan-coated, matrix metalloproteinase-responsive microgel.
- Loading of miRNA-155 into a nucleus pulposus cell (NPC)-targeted nanocarrier (NGM) via host-guest binding.
- Incorporation of SS31 into the nanogel network for mitochondrial regulation.
- Evaluation of lactic acid capture, pH-responsive release, and anti-apoptotic effects.
Main Results:
- The microgel system effectively captured lactic acid, alleviating the acidic microenvironment.
- pH-responsive release of miRNA-155 from the NGM was achieved, regulating apoptosis.
- SS31 dissociation modulated mitochondrial metabolism.
- The microgel system demonstrated significant protection of cell viability and promoted IVD regeneration.
Conclusions:
- The developed microgel system offers a promising strategy for IVD regeneration by addressing key pathological factors.
- Modulating the acidic microenvironment and preventing NPC apoptosis are critical for therapeutic success.
- This approach highlights the potential of functionalized biomaterials in treating degenerative diseases.
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