Abstract
Present study, for the first time, reports the development of a nanohybridized baculovirus based stent that can locally promote vascular re-endothelialization by efficient delivery of pro-angiogenic vascular endothelial growth factor (Vegf) genes. In vitro data demonstrated rapid expression of functionally active Vegf by the bioactive stent-transduced vascular cells. In vivo site-specific transgene expression was observed at the stented regions of balloon-denuded canine femoral artery, which eventually lead to significant endothelial recovery at the injured sites. A significant reduction in neointima formation (2.23 ± 0.56 mm2 vs 2.78 ± 0.49 mm2 and 3.11 ± 0.23 mm2, p < 0.05; n = 8) and percent stenosis was observed in treated stent group compared to negative control and bare metal stent groups. These findings collectively implicate the potential of this newly developed baculovirus based biotherapeutic stent to ameliorate damaged vascular biology and attenuate re-narrowing of stented artery by inhibiting neointima formation.
Highlights
Present study, for the first time, reports the development of a nanohybridized baculovirus based stent that can locally promote vascular re-endothelialization by efficient delivery of pro-angiogenic vascular endothelial growth factor (Vegf) genes
Transmission Electron Microcope (TEM) images in Figure S3c demonstrates the efficient binding of the rod like baculovirus with Polyamidoamine dendrimer synthetic nanoparticles (PAMAM) dendrimers (0.05) leading to the formation of Bac-PAMAM hybrid complex
To the best of our knowledge, this study for the first time demonstrates that insect cell generated recombinant baculoviruses can be efficiently used for stent based gene therapy applications, such as inhibition of post angioplasty in-stent restenosis (ISR)
Summary
For the first time, reports the development of a nanohybridized baculovirus based stent that can locally promote vascular re-endothelialization by efficient delivery of pro-angiogenic vascular endothelial growth factor (Vegf) genes. Recent studies have demonstrated the importance of such nano-biomaterials to develop new biotherapeutics which have the unique features to restore the natural vascular biology by promoting natural healing in contrary to the DES13–19 Such technologies have the unique potential to promote localized and sustained delivery of biomolecules, such as therapeutic genes, to the damaged arterial wall using the stent surface as the permanent scaffold structure and reservoir for prolonged arterial gene delivery[20,21,22]. The MS were impregnated in fibrin hydrogel and coated using layer-by-layer assembly on prefabricated stent surface[33], which eventually acts as the scaffold to deliver the protected viral nanohybrids to the target site We postulated that this new generation of gene eluting stent device can efficiently deliver angiogenic vascular genes to the affected site and induce favorable therapeutic effect in the local vascular biology as illustrated in Figure S1 to promote local wound healing. The study assessed the hypothesis by investigating the stent device efficacy using Vegf carrying recombinant baculovirus (Bacvegf) nanohybrids and control Bac carrying no gene (BacNull), followed by evaluating its potential to accelerate re-endothelialization and attenuate in-stent restenosis (ISR) in balloon injured dog femoral artery
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
