Bioactive Silk Fibroin Hydrogel Harnesses BMSCs‐EVs to Modulate Inflammatory Microenvironment in Intervertebral Disc Degeneration

Sep 4, 2025Journal of extracellular vesicles

Silk Protein Gel Uses Stem Cell Particles to Reduce Inflammation in Degenerating Spinal Discs

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

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.

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(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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Bioactive Silk Fibroin Hydrogel Harnesses BMSCs‐EVs to Modulate Inflammatory Microenvironment in Intervertebral Disc Degeneration

Abstract

Key numbers

Full Text

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