Extracellular vesicles (EVs) have emerged as promising acellular tools for modulating immune responses for tissue engineering applications. This study explores the potential of human fibroblast-derived EVs delivered within a three-dimensional (3D) injectable scaffold composed of polycaprolactone (PCL) nanofibers and collagen (PNCOL) to reprogram macrophage behavior and support scaffold integrity under inflammatory conditions. EVs were successfully isolated from human fibroblasts using ultracentrifugation and characterized for purity, size distribution and surface markers (CD63 and CD9). Macrophage-laden PNCOL scaffolds were prepared under three conditions: macrophage-only (MP), fibroblast co-encapsulated (F-MP), and EV-encapsulated (EV-MP) groups. Structural integrity was assessed via scanning electron microscopy and Masson's trichrome staining, while immunomodulatory effects were evaluated through metabolic assays, gene expression profiling, and immunohistochemistry for macrophage polarization markers (CD80, CD206). When co-encapsulated with pro-inflammatory (M1) macrophages in PNCOL scaffolds, fibroblast-derived EVs preserved scaffold structure and significantly enhanced macrophage metabolic activity compared to the control (MP) and other experimental group (F-MP). The gene expression and immunohistochemistry data demonstrated substantial upregulation of anti-inflammatory markers (TGF-β, CD163, and CCL18) and surface protein CD206, indicating a phenotypic shift toward M2-like macrophages for EV-encapsulated scaffolds relative to the other groups. The findings of this study demonstrate that fibroblast-derived EVs integrated into injectable PCL-collagen scaffolds offer a viable, cell-free approach to modulate inflammation, preserve scaffold structure, and support regenerative healing. This strategy holds significant promise for advancing immuno-instructive platforms in regenerative medicine, particularly in settings where conventional cell therapies face limitations in survival, cost, or safety.
Immunomodulation Through Fibroblast-Derived Extracellular Vesicles (EVs) Within 3D Polycaprolactone-Collagen Matrix.
阅读:3
作者:Tasnim Afsara, Jacho Diego, Rabino Agustin, Benalcazar Jose, Garcia-Mata Rafael, Lapitsky Yakov, Yildirim-Ayan Eda
期刊: | Biomimetics | 影响因子: | 3.900 |
时间: | 2025 | 起止号: | 2025 Jul 22; 10(8):484 |
doi: | 10.3390/biomimetics10080484 |
特别声明
1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。
2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。
3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。
4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。