Mechanical activation of fibroblasts, caused by friction and transforming growth factor-β1 recognition, is one of the main causes of tissue adhesions. In this study, we developed a lubricated gene-hydrogel patch, which provides both a motion lubrication microenvironment and gene therapy. The patch's outer layer is composed of polyethylene glycol polyester hydrogel. The hydrogel forms hydrogen bonds with water molecules to create the motion lubrication layer, and it also serves as a gene delivery library for long-term gene silencing. Under the motion lubricated microenvironment, extracellular signal-regulated kinase-small interfering RNA can silence fibroblasts and enhance the blocking effect against fibroblast activation. In vitro, the proposed patch effectively inhibits fibroblast activation and reduces the coefficient of friction. In vivo, this patch reduces the expression of vimentin and α-smooth muscle actin in fibroblasts. Therefore, the lubricated gene-hydrogel patch can inhibit the mechanical activation of fibroblasts to promote tendon healing.
Keyphrases
- drug delivery
- transforming growth factor
- smooth muscle
- gene therapy
- stem cells
- hyaluronic acid
- extracellular matrix
- copy number
- high speed
- epithelial mesenchymal transition
- tissue engineering
- poor prognosis
- transcription factor
- mass spectrometry
- magnetic resonance imaging
- dna methylation
- signaling pathway
- diffusion weighted imaging