Dual gene-activated dermal scaffolds regulate angiogenesis and wound healing by mediating the coexpression of VEGF and angiopoietin-1
© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers..
The vascularization of dermal substitutes is a key challenge in efforts to heal deep skin defects. In this study, dual gene-activated dermal scaffolds (DGADSs-1) were fabricated by loading nanocomposite particles of polyethylenimine (PEI)/multiple plasmid DNAs (pDNAs) encoding vascular endothelial growth factor and angiopoietin-1 at a ratio of 1:1. In a similar manner, DGADSs-2 were loaded with a chimeric plasmid encoding both VEGF and Ang-1. In vitro studies showed that both types of DGADSs released PEI/pDNA nanoparticles in a sustained manner; they demonstrated effective transfection ability, leading to upregulated expression of VEGF and Ang-1. Furthermore, both types of DGADSs promoted fibroblast proliferation and blood vessel formation, although DGADSs-1 showed a more obvious promotion effect. A rat full-thickness skin defect model showed that split-thickness skin transplanted using a one-step method could achieve full survival at the 12th day after surgery in both DGADSs-1 and DGADSs-2 groups, and the vascularization time of dermal substitutes was significantly shortened. Compared with the other three groups of scaffolds, the DGADSs-1 group had significantly greater cell infiltration, collagen deposition, neovascularization, and vascular maturation, all of which promoted wound healing. Thus, compared with single-gene-activated dermal scaffolds, DGADSs show greater potential for enhancing angiogenesis. DGADSs with different loading modes also exhibited differences in terms of angiogenesis; the effect of loading two genes (DGADSs-1) was better than the effect of loading a chimeric gene (DGADSs-2). In summary, DGADSs, which continuously upregulate VEGF and Ang-1 expression, offer a new functional tissue-engineered dermal substitute with the ability to activate vascularization.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Bioengineering & translational medicine - 8(2023), 5 vom: 24. Sept., Seite e10562 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Weng, Tingting [VerfasserIn] |
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| Links: |
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| Themen: |
Angiogenesis |
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| Anmerkungen: |
Date Revised 13.09.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1002/btm2.10562 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The vascularization of dermal substitutes is a key challenge in efforts to heal deep skin defects. In this study, dual gene-activated dermal scaffolds (DGADSs-1) were fabricated by loading nanocomposite particles of polyethylenimine (PEI)/multiple plasmid DNAs (pDNAs) encoding vascular endothelial growth factor and angiopoietin-1 at a ratio of 1:1. In a similar manner, DGADSs-2 were loaded with a chimeric plasmid encoding both VEGF and Ang-1. In vitro studies showed that both types of DGADSs released PEI/pDNA nanoparticles in a sustained manner; they demonstrated effective transfection ability, leading to upregulated expression of VEGF and Ang-1. Furthermore, both types of DGADSs promoted fibroblast proliferation and blood vessel formation, although DGADSs-1 showed a more obvious promotion effect. A rat full-thickness skin defect model showed that split-thickness skin transplanted using a one-step method could achieve full survival at the 12th day after surgery in both DGADSs-1 and DGADSs-2 groups, and the vascularization time of dermal substitutes was significantly shortened. Compared with the other three groups of scaffolds, the DGADSs-1 group had significantly greater cell infiltration, collagen deposition, neovascularization, and vascular maturation, all of which promoted wound healing. Thus, compared with single-gene-activated dermal scaffolds, DGADSs show greater potential for enhancing angiogenesis. DGADSs with different loading modes also exhibited differences in terms of angiogenesis; the effect of loading two genes (DGADSs-1) was better than the effect of loading a chimeric gene (DGADSs-2). In summary, DGADSs, which continuously upregulate VEGF and Ang-1 expression, offer a new functional tissue-engineered dermal substitute with the ability to activate vascularization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a VEGF | |
| 650 | 4 | |a angiogenesis | |
| 650 | 4 | |a angiopoietin‐1 | |
| 650 | 4 | |a dual gene‐activated scaffolds | |
| 650 | 4 | |a wound healing | |
| 700 | 1 | |a Yang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Ronghua |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Sizhan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Manjia |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Pan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiaojie |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Chunmao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xiong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xingang |e verfasserin |4 aut | |
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