Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration.

Vascularization remains a critical challenge in dermal tissue regeneration. In this study, a vascular endothelial growth factor (VEGF165) and angiopoietin-1 (Ang-1) dual gene co-expression vector that encoded green fluorescent protein (GFP) was constructed from an Arg-Gly-Asp-modified adenovirus. Silk fibroin (SF) scaffolds loaded with adenovirus vectors were fabricated by freeze-drying method. In vitro, the human endothelial-derived cell line EA.hy926 was infected with adenovirus vectors and then expressed GFP, secreted VEGF165 and Ang-1, and promoted cell proliferation effectively. The VEGF165 and Ang-1 genes loaded in the SF scaffolds significantly promoted the formation of abundant microvascular networks in the chick embryo chorioallantoic membrane. In vivo, angiogenic genes loaded in the scaffolds promoted vascularisation and collagen deposition in scaffolds, thus effectively accelerating dermal tissue regeneration in a dorsal full-thickness skin defect wound model in Sprague-Dawley rats. In conclusion, SF scaffolds loaded with Arg-Gly-Asp-modified adenovirus vectors encoding VEGF165 and Ang-1 could stimulate the formation of vascular networks through the effective expression of target genes in vascular endothelial cells, thereby accelerating the regeneration of dermal tissue.