Silk fibroin hydrogel loaded with S100B-enriched may improve outcomes.
Intervertebral disc degeneration is associated with inflammation and impaired mobility.
Silk fibroin hydrogel acts as a biocompatible carrier for mRNA-engineered extracellular vesicles.
In vitro, the hydrogel complex inhibited inflammatory and promoted healing markers.
In vivo, implantation of the hydrogel improved disc structure and reduced macrophage inflammation.
High-throughput RNA sequencing identified S100B as a significant factor in modulating inflammation.
Simplified
(IVDD) is a common age-related disorder associated with inflammation, pain and impaired mobility. In this study, we developed a therapeutic system using silk fibroin (SF) hydrogel loaded with mRNA-engineered derived from murine bone marrow mesenchymal stem cells (BMSCs-EVs) to modulate and alleviate IVDD. BMSCs were isolated from 6-week-old C57BL/6 mice, and an acute IVDD model was established via 18G needle puncture of the coccygeal discs (Co7-Co10). RAW 264.7 murine macrophages were used for in vitro assays, with M1 polarization induced by LPS and IFN-γ. The SF/EVs complex was characterized by SEM, FTIR and rheology, confirming its structural suitability for EV delivery. Functionally, SF hydrogel not only served as a biocompatible carrier but also enabled sustained release of EVs, enhancing their anti-inflammatory effects. In vitro, SF/EVs inhibited M1 polarization and promoted M2 marker expression. In vivo implantation improved disc histology and reduced inflammatory macrophage infiltration. High-throughput RNA sequencing identified S100B as a key functional cargo within EVs. Lentivirus-mediated overexpression and knockdown experiments confirmed that EV-derived S100B suppresses M1 polarization and mitigates IVDD progression. In summary, SF hydrogel loaded with S100B-enriched BMSCs-EVs offers a promising strategy to reshape the inflammatory microenvironment and promote disc regeneration in IVDD.
Key numbers
DHI improvement in group
DHI Change
Measured by X-ray imaging after 8 weeks of treatment.
Reduction in expression
Inflammatory Marker Reduction
Assessed by immunofluorescence in treated mice.
252 differentially expressed genes identified
Gene Expression Changes
Compared between control and -treated groups.
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