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Silencing Gene-Engineered Injectable Hydrogel Microsphere for Regulation of Extracellular Matrix Metabolism Balance
Hongze Chang1,2, Feng Cai1, Yan Zhang1
1Department of Orthopedics, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, P. R. China.
Small Methods
|January 7, 2022
Summary
This study developed injectable microspheres to silence pathological genes in nucleus pulposus cells, restoring extracellular matrix balance and inhibiting intervertebral disc degeneration in a rat model.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Gene Therapy
Background:
- Maintaining extracellular matrix (ECM) metabolism balance is crucial for tissue integrity.
- Abnormal microenvironments challenge long-term ECM balance, leading to tissue degeneration.
- Intervertebral disc (IVD) degeneration involves complex cellular and microenvironmental crosstalk.
Purpose of the Study:
- To develop an injectable gene-silencing system for regulating ECM metabolism in nucleus pulposus (NP) cells.
- To inhibit intervertebral disc (IVD) degeneration by restoring ECM balance in a nutrient-restricted environment.
- To investigate the potential of circRNA silencing-hydrogel microspheres for targeted gene delivery.
Main Methods:
- Constructed injectable circRNA silencing-hydrogel microspheres (psh-circSTC2-lipo@MS) using methacrylated hyaluronic acid (HAMA) and liposomes.
- Grafted circSTC2 silencing genes-loaded DOTAP/Chol/DOPE cationic liposomes onto HAMA microspheres.
- Evaluated microsphere properties (degradability, swellability, injectability) and lipoplex release kinetics.
- Assessed the effect of psh-circSTC2-lipo@MS on NP cells in vitro under nutrient-restricted conditions.
- In vivo testing in a rat IVD nutrient-restricted model.
Main Results:
- HAMA microspheres exhibited favorable degradability, swellability, and injectability.
- Lipoplexes demonstrated efficient loading and sustained release for 27 days.
- psh-circSTC2-lipo@MS significantly promoted ECM protein synthesis and inhibited ECM catabolism in NP cells.
- In vivo, local injection of psh-circSTC2-lipo@MS promoted ECM synthesis and restored NP tissue in rats.
- The system showed efficient gene silencing in NP cells.
Conclusions:
- Injectable psh-circSTC2-lipo@MS effectively regulates ECM metabolism balance in nutrient-restricted NP cells.
- This targeted gene delivery system shows significant potential for inhibiting IVD degeneration.
- The developed microspheres represent a safe and controllable approach for treating ECM-related tissue disorders.
