期刊
BIOMATERIALS SCIENCE
卷 9, 期 6, 页码 2067-2081出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm01560a
关键词
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资金
- GENE2SKIN Twinning Project Horizon 2020 (European Commission) [692221]
- Dressing4Scars [M-ERA-NET2/0013/2016]
- Science Foundation Ireland [16/M-ERA/3420]
- Health Research Board [ILP-POR-2017-032]
- Discoveries Centre for Regenerative and Precision Medicine [H2020-WIDESPREAD-2014-1-739572]
- [NORTE-08-5369-FSE-000037]
- Science Foundation Ireland (SFI) [16/M-ERA/3420] Funding Source: Science Foundation Ireland (SFI)
- Health Research Board (HRB) [ILP-POR-2017-032] Funding Source: Health Research Board (HRB)
Delivery of genes encoding angiogenic growth factors to cells in a scaffold microenvironment can lead to controlled release of angiogenic proteins promoting vascularization and providing structural support for new matrix deposition.
Vascularization is still one of the major challenges in tissue engineering. In the context of tissue regeneration, the formation of capillary-like structures is often triggered by the addition of growth factors which are associated with high cost, bolus release and short half-life. As an alternative to growth factors, we hypothesized that delivering genes-encoding angiogenic growth factors to cells in a scaffold microenvironment would lead to a controlled release of angiogenic proteins promoting vascularization, simultaneously offering structural support for new matrix deposition. Two non-viral vectors, chitosan (Ch) and polyethyleneimine (PEI), were tested to deliver plasmids encoding for vascular endothelial growth factor (pVEGF) and fibroblast growth factor-2 (pFGF2) to human dermal fibroblasts (hDFbs). hDFbs were successfully transfected with both Ch and PEI, without compromising the metabolic activity. Despite low transfection efficiency, superior VEGF and FGF-2 transgene expression was attained when pVEGF was delivered with PEI and when pFGF2 was delivered with Ch, impacting the formation of capillary-like structures by primary human dermal microvascular endothelial cells (hDMECs). Moreover, in a 3D microenvironment, when PEI-pVEGF and Ch-FGF2 were delivered to hDFbs, cells produced functional pro-angiogenic proteins which induced faster formation of capillary-like structures that were retained in vitro for longer time in a Matrigel assay. The dual combination of the plasmids resulted in a downregulation of the production of VEGF and an upregulation of FGF-2. The number of capillary-like segments obtained with this system was inferior to the delivery of plasmids individually but superior to what was observed with the non-transfected cells. This work confirmed that cell-laden scaffolds containing transfected cells offer a novel, selective and alternative approach to impact the vascularization during tissue regeneration. Moreover, this work provides a new platform for pathophysiology studies, models of disease, culture systems and drug screening.
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