Dual gene‐activated dermal scaffolds regulate angiogenesis and wound healing by mediating the coexpression of VEGF and angiopoietin‐1

Author:

Weng Tingting123,Yang Min12,Zhang Wei12,Jin Ronghua12,Xia Sizhan12,Zhang Manjia4,Wu Pan12,He Xiaojie12,Han Chunmao12ORCID,Zhao Xiong3,Wang Xingang12ORCID

Affiliation:

1. Department of Burns & Wound Care Centre Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China

2. The Key Laboratory of Severe Trauma and Burns of Zhejiang Province Hangzhou China

3. Department of Burn and Plastic Surgery Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center Hangzhou China

4. The First Clinical Medical College, Zhejiang Chinese Medical University Hangzhou China

Abstract

AbstractThe 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.

Funder

Basic Public Welfare Research Program of Zhejiang Province

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biotechnology

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