| Mechanical stress in GelMA/fibrin scaffolds promotes angiogenesis by influencing fibroblast-derived exosome secretion |
| 论文作者 |
Wan, JM; Du, T; Liu, ZH; Xu, C; Yu, SY; Zhang, ZQ; Ji, PX; Le, YY; Zhang, GL; Hou, RX |
| 期刊/会议名称 |
MATERIALS TODAY COMMUNICATIONS |
| 论文年度 |
2025 |
| 论文类别 |
|
| 摘要 |
Angiogenesis is critical for the success of tissue-engineered dermis (TED) in regenerative medicine; however, the mechanisms regulating this process remain poorly understood. Mechanical stress is a key environmental factor that enhances the secretion of human dermal fibroblast-derived exosomes (HDF-Exo) secretion, which may influence angiogenesis. In this study, we investigated the role of mechanical stress in promoting angiogenesis in TED, using HDF-Exos. A novel biological scaffold was used to culture fibroblasts in TED constructs under mechanical stress. The secretion of exosomes was measured and their effects on human umbilical vein endothelial cells were evaluated for their angiogenic potential. The protein profiles of exosomes were analysed using mass spectrometry and the role of exosomes was confirmed using the GW4869 inhibitor, which blocks exosome secretion. Mechanical stress significantly increased HDF-Exo secretion and promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tubular structure formation. Mass spectrometry revealed a distinct protein profile in mechanically stimulated exosomes, including upregulation of pro-angiogenic factors. GW4869 treatment inhibited capillary formation within the TED constructs, confirming the importance of exosomes in vascularisation. Pathway analysis highlighted the involvement of signalling pathways, such as Rho protein signalling and the MAPK cascade, with Yes-associated proteins playing a pivotal role in mediating the effects of mechanical stress on exosome secretion and angiogenesis. This study demonstrated that mechanical stress enhances the secretion of HDF-Exo, which promotes angiogenesis within TED. These findings provide insights into the molecular mechanisms of TED vascularisation and suggest that combining mechanical stress with exosome-based therapies can optimise tissue-engineered skin for regenerative medicine. Further research is needed to validate these results in vivo and explore the specific molecular pathways involved. |
| 卷 |
44 |
| 影响因子 |
4.5 |
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