Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing

He, Shan1,2; Fang, Ju1; Zhong, Chuanxin1; Ren, Fuzeng1; Wang, Min2

2022-03-01

10.1016/j.actbio.2021.11.037

Acta Biomaterialia   影响因子和分区

1742-7061

1878-7568

Regulating cell function and tissue formation by combining gene delivery with functional scaffolds to cre-ate gene-activated matrices (GAMs) is a promising strategy for tissue engineering. However, fabrication of GAMs with low cytotoxicity, high transfection efficiency, and long-term gene delivery properties re-mains a challenge. In this study, a non-viral DNA delivery nanocomplex was developed by modifying poly (D, L-lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) nanoparticles with the cell-penetrating peptide KALA. Subsequently, the nanocomplex carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF) was immobilized onto a polydopamine-coated electrospun alginate nanofibrous scaffold, result-ing in a GAM for enhanced skin wound healing. The nanocomplex exhibited much lower cytotoxicity and comparable or even higher transfection efficiency compared with PEI. The GAM enabled sustained gene release and long-tern transgene expression of VEGF in vitro . In an excisional full-thickness skin wound rat model, the GAM could accelerate wound closure, promote complete re-epithelization, reduce inflam-matory response, and enhance neovascularization, ultimately enhancing skin wound healing. The current GAM comprising a low-toxic gene delivery nanocomplex and a biocompatible 3D nanofibrous scaffold demonstrates great potential for mediating long-term cell functions and may become a powerful tool for gene delivery in tissue engineering.Statement of significanceGene delivery is a promising strategy in promoting tissue regeneration as an effective alternative to growth factor delivery, but the study on three-dimensional gene-activated scaffolds remains in its infancy. Herein, a biodegradable nanofibrous gene-activated matrix integrating non-viral nanoparticle vector was designed and evaluated both in vitro and in vivo. The results show that the nanoparticle vector provided high transfection efficiency with minimal cytotoxicity. After surface immobilization of the nanocomplexes carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF), the nanofibrous scaffold en-abled sustained DNA release and long-term transgene expression in vitro . In a rat full-thickness skin wound model, the scaffold could accelerate wound healing. This innovative gene-activated matrix can be a promising candidate for tissue regeneration.(c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gene-activated matrix Non-viral vector Nanofiber Vascular endothelial growth factor Wound healing

SCI ; EI

英语

第一 ; 通讯

National Key Research and Development Program of China[2016YFB0700803] ; Fundamental Research Program of Shenzhen[JCYJ20190809140401658]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000753474800009

ELSEVIER SCI LTD

20215111354949

Biocompatibility ; Biomolecules ; Cell engineering ; Cytotoxicity ; DNA ; Efficiency ; Encoding (symbols) ; Endothelial cells ; Gene encoding ; Nanofibers ; Nanoparticles ; Peptides ; Rats ; Scaffolds (biology) ; Signal encoding ; Tissue ; Tissue regeneration ; Vectors

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Genetic Engineering:461.8.1 ; Biology:461.9 ; Immunology:461.9.1 ; Information Theory and Signal Processing:716.1 ; Data Processing and Image Processing:723.2 ; Nanotechnology:761 ; Biochemistry:801.2 ; Production Engineering:913.1 ; Algebra:921.1 ; Solid State Physics:933

Web of Science

1.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen, Guangdong, Peoples R China
2.Univ Hong Kong, Dept Mech Engn, Pokfulam Rd, Hong Kong, Peoples R China

He, Shan,Fang, Ju,Zhong, Chuanxin,et al. Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing[J]. Acta Biomaterialia,2022,140:149-162.

He, Shan,Fang, Ju,Zhong, Chuanxin,Ren, Fuzeng,&Wang, Min.(2022).Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing.Acta Biomaterialia,140,149-162.

He, Shan,et al."Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing".Acta Biomaterialia 140(2022):149-162.