Angiogenic Modification of Microfibrous Polycaprolactone by pCMV-VEGF165 Plasmid Promotes Local Vascular Growth after Implantation in Rats

Abstract

Insufficient vascular growth in the area of artificial-material implantation contributes to ischemia, fibrosis, the development of bacterial infections, and tissue necrosis around the graft. The purpose of this study was to evaluate angiogenesis after implantation of polycaprolactone microfiber scaffolds modified by a pCMV-VEGF165-plasmid in rats. Influence of vascularization on scaffold degradation was also examined. We investigated flat microfibrous scaffolds obtained by electrospinning polycaprolactone with incorporation of the pCMV-VEGF-165 plasmid into the microfibers at concentrations of 0.005 ng of plasmid per 1 mg of polycaprolactone (0.005 ng/mg) (LCGroup) and 0.05 ng/mg (HCGroup). The samples were subcutaneously implanted in the interscapular area of rats. On days 7, 16, 33, 46, and 64, the scaffolds were removed, and a histological study with a morphometric evaluation of the density and diameter of the vessels and microfiber diameter was performed. The number of vessels was increased in all groups, as well as the resorption of the scaffold. On day 33, the vascular density in the HCGroup was 42% higher compared to the control group (p = 0.0344). The dose-dependent effect of the pCMV-VEGF165-plasmid was confirmed by enhanced angiogenesis in the HCGroup compared to the LCGroup on day 33 (p-value = 0.0259). We did not find a statistically significant correlation between scaffold degradation rate and vessel growth (the Pearson correlation coefficient was ρ = 0.20, p-value = 0.6134). Functionalization of polycaprolactone by incorporation of the pCMV-VEGF165 plasmid provided improved vascularization within 33 days after implantation, however, vessel growth did not seem to correlate with scaffold degradation rate.

Overview of Electrospinning for Tissue Engineering Applications

“…Klabukov et al explored flat microfibrous scaffolds obtained by electrospinning polycaprolactone with the incorporation of the pCMV-VEGF-165 plasmid into the microfibres at concentrations of 0.005 ng of plasmid per 1 mg of polycaprolactone (0.005 ng/mg) (LCGroup) and 0.05 ng/mg (HCGroup) [85]. The results demonstrated that pCMV-VEGF165 plasmid functionalisation of polycaprolactone led to better vascularisation 33 days after implantation; however, vessel growth did not appear to be correlated with scaffold degradation rate [85].…”

Biomechanical Behaviors and Degradation Properties of Multilayered Polymer Scaffolds: The Phase Space Method for Bile Duct Design and Bioengineering

“…The design of smart scaffolds for the creation of tissue-engineered grafts requires not only new materials and methods for their modification [ 120 ], but also quantitative models for the assessment of their physiological relevance [ 121 , 122 ]. Therefore, the design of tissue-engineered grafts that fulfill clinical requirements remains a grand challenge for the creation of physiologically relevant tissue-engineered organs and tissues.…”

Electrospinning Processing of Polymer/Nanocarbon Nanocomposite Nanofibers—Design, Features, and Technical Compliances

“…On the other hand, coaxial electrospinning definitely varies from the emulsion-based method as it produces higher-mechanical-strength fibers. In tissue engineering, coaxial-produced nanofibers revealed better cell attachment and proliferation due to a core-sheath nanostructure [61]. However, both coaxial and emulsion electrospinning form nanofibers having an outer sheath and inner core.…”