Injectable Silk Fibroin/Tannic Acid Hydrogel with Dual Factors for Meniscus Repair.
basic_science · Level V
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- Record sourced from PubMed, PMID 42175907.
- Also identified by DOI 10.1177/19373341261449878.
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Abstract
Despite advances in tissue engineering, the clinical application of scaffolds for meniscal repair remains limited by implantation challenges and the difficulty of directing stem cells toward a stable meniscal phenotype. Here, we present an injectable hydrogel composed of silk fibroin (SF) and tannic acid (TA), codelivering transforming growth factor-β<sub>3</sub> (TGF-β<sub>3</sub>) and the transcription factor Mohawk (MKX). TA enhanced the β-sheet content of SF, yielding a hydrogel with superior rheological stability and shear-thinning behavior suitable for minimally invasive administration. The ST hydrogel provided sustained release of both bioactive factors over 35 days, with cumulative release below 16%. MKX attenuated TGF-β<sub>3</sub>-induced hypertrophic differentiation of adipose-derived mesenchymal stem cells, promoting a fibrochondrocyte-like phenotype characterized by elevated expression of <i>COL1A1</i>, <i>COL2A1</i>, and aggrecan. Inflammatory stimulation assays demonstrated downregulation of osteoarthritis-related genes (e.g., <i>MMP13</i>, <i>IL-6</i>, and <i>RUNX2</i>) in the ST-TM group. In a rabbit meniscus tear model, ST hydrogels loaded with TGF-β<sub>3</sub> and MKX significantly enhanced extracellular matrix deposition, promoted structural repair of the meniscus, and improved biomechanical properties at 10 weeks postimplantation. These findings support the potential of this dual-factor hydrogel system as a cell-free therapeutic strategy for functional meniscus regeneration, with potential relevance to the modulation of OA-related degeneration.Impact StatementThis study presents a novel injectable silk fibroin/tannic acid hydrogel codelivering transforming growth factor-β<sub>3</sub> and Mohawk, which synergistically promotes fibrochondrocyte differentiation and inhibits hypertrophy of stem cells. Demonstrating injectable handling characteristics, controlled release, and <i>in vivo</i> efficacy, this cell-free platform offers a clinically translatable strategy for functional meniscus repair, with potential protective effects against osteoarthritis-related degeneration.