Gene‐Hydrogel Microenvironment Regulates Extracellular Matrix Metabolism Balance in Nucleus Pulposus

Abstract: Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Gene‐Hydrogel Microenvironment Regulates Extracellular Matrix Metabolism Balance in Nucleus Pulposus ; volume:7 ; number:1 ; year:2020 ; extent:10
Advanced science ; 7, Heft 1 (2020) (gesamt 10)

Creator
Chen, Wei
Chen, Hao
Zheng, Dandan
Zhang, Hongbo
Deng, Lianfu
Cui, Wenguo
Zhang, Yuhui
Santos, Hélder A.
Shen, Hongxing

DOI
10.1002/advs.201902099
URN
urn:nbn:de:101:1-2022062411263991281466
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:36 AM CEST

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