Introduction: We recently showed that a decellularized leaf scaffold can be loaded with polylactic-co-
glycolic acid (PLGA)-based
rapamycin nanoparticles, this leaf patch can then inhibit venous neointimal
hyperplasia in a rat inferior vena cava (IVC) venoplasty model.
IL-33 plays a role in the neointimal formation after
vascular injury. We hypothesized that plant leaves can absorb therapeutic
drug solution and can be used as a patch with
drug delivery capability, and plant leaves absorbed with
IL-33 antibody can decrease venous neointimal
hyperplasia in the rat IVC venoplasty model. Method: A human spiral saphenous vein (SVG) graft implanted in the popliteal vein was harvested from a patient with
trauma and analyzed by immunofluorescence. Male Sprague-Dawley rats (aged 6-8 weeks) were used to create the IVC patch venoplasty model. Plant leaves absorbed with
rhodamine, distilled water (control),
rapamycin,
IL-33, and
IL-33 antibody were cut into patches (3 × 1.5 mm2) and implanted into the rat IVC. Patches were explanted at day 14 for analysis. Result: At day 14, in the patch absorbed with
rhodamine group, immunofluorescence showed
rhodamine fluorescence in the
neointima, inside the patch, and in the adventitia. There was a significantly thinner
neointima in the plant patch absorbed with
rapamycin (p = 0.0231) compared to the patch absorbed with distilled water. There was a significantly large number of
IL-33 (p = 0.006) and IL-1β (p = 0.012) positive cells in the human SVG
neointima compared to the human great saphenous vein. In rats, there was a significantly thinner
neointima, a smaller number of
IL-33 (p = 0.0006) and IL-1β (p = 0.0008) positive cells in the
IL-33 antibody-absorbed patch group compared to the IL-33-absorbed patch group. Conclusion: We found that the natural absorption capability of plant leaves means they can absorb
drug solution efficiently and can also be used as a novel drug delivery system and venous patch.
IL-33 plays a role in venous neointimal
hyperplasia both in humans and rats; neutralization of
IL-33 by
IL-33 antibody can be a therapeutic method to decrease venous neointimal
hyperplasia.