Silk fibroin hydrogel adhesive combined with miR-455 modified framework nucleic acids/ROS-responsive CeO2 nanozymes for meniscus tears reconstruction

TL;DR

A new hydrogel system combining silk fibroin, nanozymes, and miRNA-455 is developed to repair meniscus tears and promote cartilage regeneration.

Contribution

A multifunctional composite hydrogel system is introduced for meniscus repair, integrating SilMA, CeO2 nanozymes, and tFNA-miR-455 for structural and biological support.

Findings

The SilMA hydrogel provides injectability, tissue adhesion, and mechanical support for meniscus repair.

CeO2 nanozymes reduce inflammation by scavenging ROS and creating a regeneration-friendly environment.

tFNA-miR-455 delivery promotes chondrogenic differentiation of stem cells, enhancing fibrocartilage formation.

Abstract

The meniscus, a critical fibrocartilaginous structure in the knee joint that cushions load and stabilizes movement, suffers from poor self-healing potential following tears. This impaired repair not only fails to restore joint function but often progresses to osteoarthritis, posing significant clinical challenges. Regrettably, current therapeutic approaches, such as surgical suturing or partial resection, have limited efficacy in achieving functional regeneration of the meniscus. To address these bottlenecks, we developed a multifunctional composite hydrogel system integrating methacrylated silk fibroin (SilMA), cerium dioxide (CeO2) nanozymes and tetrahedral framework nucleic acid (tFNA)-miRNA-455. The SilMA hydrogel, leveraging photocrosslinking technology for on-demand solidification, offers injectability (enabling minimally invasive delivery), strong tissue adhesion and robust mechanical support—effectively bridging meniscal tear gaps and creating a scaffold for cell infiltration. Embedded CeO2 nanozymes act as potent reactive oxygen species (ROS) scavengers and nanozyme-mediated ROS clearance mitigates inflammation and fosters a regeneration-conducive microenvironment. Moreover, tFNAs serve as a biocompatible, stable delivery vector for miRNA-455, protecting the nucleic acid from degradation and ensuring its efficient cellular uptake. This targeted delivery drives chondrogenic differentiation of synovial mesenchymal stem cells (SMSCs), directly promoting fibrocartilage formation. This synergistic strategy unites structural reinforcement, immunomodulation and stem cell regulation, overcoming conventional carrier limitations (cytotoxicity and poor stability) and demonstrating significant potential for meniscal repair. Ultimately, it offers a promising solution for cartilage regeneration and meniscus function restoration, with broad implications for clinical translation.

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