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

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.

Klabukov Ilya 1, 2 , Balyasin Maksim 2 , Krasilnikova Olga1 , Tenchurin Timur3 , Titov Alexander4 , Krasheninnikov Mikhail 2, 5 , Mudryak Daniil4, 5 , Sulina Yana5 , Shepelev Alexey3 , Chvalun Sergei3 , Dyuzheva Tatiana6 , Yakimova Anna7 , Sosin Dmitry8 , Lyundup Alexey 2 , Baranovskii Denis 2, 7 , Shegay Peter 1, 2 , Kaprin Andrey 1, 2
Номер выпуска
  • 1 National Medical Research Radiological Center
  • 2 Peoples’ Friendship University Of Russia
  • 3 National Research Centre “Kurchatov Institute”
  • 4 City Clinical Hospital No. 67 of Moscow Health Department
  • 5 Lomonosov Institute of Fine Chemical Technologies, Russian Technological University MIREA
  • 6 Sechenov University
  • 7 A. Tsyb Medical Research Radiological Center—Branch of the National Medical Research Radiological Center
  • 8 Center for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency
Ключевые слова
angiogenesis; material functionalization; electrospinning; gene-activated scaffold; Neovasculgen; physiological relevance; polycaprolactone; regenerative medicine; tissue engineering; vascularization
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