“…In this study, to induce the formation of new blood vessels and to promote the reconstruction of a mature vascular network, both the VEGF165 and Ang‐1 genes were selected and loaded into SF scaffolds to infect cells and coexpress bioactive VEGF165 and Ang‐1 in situ. Although gene‐activated scaffolds with nonviral gene vectors present the potential to promote vascularization, the low transfection efficiency of nonviral vectors has limited their therapeutic application (Oliveira, Rosa da Costa, & Silva, ; Reckhenrich et al, ; Wang et al, ). Recombinant adenoviruses have been used for gene therapy without integration into the host system (Appaiahgari & Vrati, ; F. C. Zhu et al, ).…”
Section: Discussionmentioning
confidence: 99%
“…Lack of vascularization is one of the major problems leading to low regeneration rates in scaffold‐dependent tissue engineering (Frueh, Menger, Lindenblatt, Giovanoli, & Laschke, ; Reckhenrich et al, ). Engineered tissue needs a vascular network to supply cells with oxygen and nutrients after the implantation of scaffolds (Novosel, Kleinhans, & Kluger, ; Rouwkema & Khademhosseini, ).…”
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 coexpression vector that encoded green fluorescent protein (GFP) was constructed from an arginine–glycine–aspartic acid‐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 vascularization 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 arginine–glycine–aspartic acid‐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.
“…In this study, to induce the formation of new blood vessels and to promote the reconstruction of a mature vascular network, both the VEGF165 and Ang‐1 genes were selected and loaded into SF scaffolds to infect cells and coexpress bioactive VEGF165 and Ang‐1 in situ. Although gene‐activated scaffolds with nonviral gene vectors present the potential to promote vascularization, the low transfection efficiency of nonviral vectors has limited their therapeutic application (Oliveira, Rosa da Costa, & Silva, ; Reckhenrich et al, ; Wang et al, ). Recombinant adenoviruses have been used for gene therapy without integration into the host system (Appaiahgari & Vrati, ; F. C. Zhu et al, ).…”
Section: Discussionmentioning
confidence: 99%
“…Lack of vascularization is one of the major problems leading to low regeneration rates in scaffold‐dependent tissue engineering (Frueh, Menger, Lindenblatt, Giovanoli, & Laschke, ; Reckhenrich et al, ). Engineered tissue needs a vascular network to supply cells with oxygen and nutrients after the implantation of scaffolds (Novosel, Kleinhans, & Kluger, ; Rouwkema & Khademhosseini, ).…”
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 coexpression vector that encoded green fluorescent protein (GFP) was constructed from an arginine–glycine–aspartic acid‐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 vascularization 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 arginine–glycine–aspartic acid‐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.
“…On placing the collagen scaffold with COPROGs on the wound bed, the infiltrated cells on the scaffold became transfected with COPROGs and started to synthesize and to release VEGF. 49 …”
Nanotechnology has considerably accelerated the growth of regenerative medicine in recent years. Application of nanotechnology in regenerative medicine has revolutionized the designing of grafts and scaffolds which has resulted in new grafts/scaffold systems having significantly enhanced cellular and tissue regenerative properties. Since the cell–cell and cell-matrix interaction in biological systems takes place at the nanoscale level, the application of nanotechnology gives an edge in modifying the cellular function and/or matrix function in a more desired way to mimic the native tissue/organ. In this review, we focus on the nanotechnology-based recent advances and trends in regenerative medicine and discussed under individual organ systems including bone, cartilage, nerve, skin, teeth, myocardium, liver and eye. Recent studies that are related to the design of various types of nanostructured scaffolds and incorporation of nanomaterials into the matrices are reported. We have also documented reports where these materials and matrices have been compared for their better biocompatibility and efficacy in supporting the damaged tissue. In addition to the recent developments, future directions and possible challenges in translating the findings from bench to bedside are outlined.
“…Common approaches to enhance vascularization in scaffolds include the use of recombinant pro-angiogenic growth factors [13], gene vectors encoding for therapeutic molecules [14] and stem cells, which may contribute to vascularization by direct differentiation into vascular structures [15] or through the secretion of paracrine factors [16]. All these approaches are promising in accelerating vascularization, but even under optimal conditions, reestablishment of proper oxygen levels through vascular supply would requires several days or weeks.…”
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