Decellularized fish swim bladder patch loaded with mesenchymal stem cells inhibits neointimal hyperplasia.

We previously showed decellularized fish swim bladder can be used as vascular patch and tube graft in rats, mesenchymal stem cells (MSCs) have showed the capability to inhibit neointimal hyperplasia in different animal models. We hypothesized that decellularized fish swim bladder patch loaded with MSCs (bioinspired patch) can inhibit neointimal hyperplasia in a rat aortic patch angioplasty model. Rat MSCs were grown in vitro and flow cytometry was used to confirm their quality. 3.6 × 105 MSCs were mixed into 100 µl of sodium alginate (SA)/hyaluronic acid (HA) hydrogel, two layers of fish swim bladders (5 mm × 5 mm) were sutured together, bioinspired patch was created by injection of hydrogel with MSCs into the space between two layers of fish swim bladder patches. Decellularized rat thoracic aorta patch was used as control. Patches were harvested at days 1 and 14 after implantation. Samples were examined by histology, immunohistochemistry, and immunofluorescence. The decellularized rat thoracic aorta patch and the fish swim bladder patch had a similar healing process after implantation. The bioinspired patch had a similar structure like native aorta. Bioinspired patch showed a decreased neointimal thickness (p = .0053), fewer macrophages infiltration (p = .0090), and lower proliferation rate (p = .0291) compared to the double layers fish swim bladder patch group. Decellularized fish swim bladder patch loaded with MSCs can inhibit neointimal hyperplasia effectively. Although this is a preliminary animal study, it may have a potential application in large animals or clinical research.

A Novel Plant Leaf Patch Absorbed With IL-33 Antibody Decreases Venous Neointimal hyperplasia.

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-1ß (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-1ß (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.