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Spontaneous Endothelialization And Biostability Of A Nanocomposite Small Caliber Bypass Graft In An Ovine Model Translates To Long Term Patency

Sandip Sarkar¹, Colin A Hart¹, Jalaledin Razaz¹, Alexander M Seifalian¹, George Hamilton² ∙ ¹Royal Free and University College Medical School, University College London, London, United Kingdom; ²Royal Free Hospital NHS Trust, London, United Kingdom

Objective(s): A poly(carbonate-urea) urethane/polyhedral oligomeric silsesquioxane nanocomposite polymer was developed and shown in vitro to be biocompatible, biostable and anti-thrombogenic. We hypothesized that compliant, caliber-matched grafts manufactured from this polymer would have long-term patency in an ovine model with similar thrombogenicity to humans and not known to self-endothelialize synthetic bypass grafts. Methods: 4mm microporous compliant grafts were interposed in the right carotid of 8 sheep. Blood flow was measured before and after implantation using duplex. After up to 662 days the grafts were explanted and examined for healing macroscopically, by microscopy and SEM. To assess mechanical integrity, burst pressures were determined and compliance was measured using wall-tracking ultrasound and a biomimetic flow circuit. ATM-FTIR was used to assess chemical degradation. Results: Carotid blood flow after implantation was 0.79 to 1.05 times pre-implantation levels. 2 animals were excluded as they died with patent grafts due to pulmonary complications. The remaining grafts were explanted after 523-662 days. Fibrous capsule surrounded the grafts. One was occluded with thrombus and another stenosed with neointimal hyperplasia. The remainder were fully patent and thrombus-free. Histology demonstrated a thin cellular lumen lining which stained positive for vWF and CD31. Neo-capillary infiltration of the graft pores from within the lumen was also identified by immunostaining. SEM confirmed a smooth lining of flattened endothelial cells over the microporous surface. The fibrous capsule increased burst pressure from 357.5mmHg (SD 15.4mmHg; n=6) to 874mmHg and reduced radial compliance from 5 to 1.8 % / mmHg x 10-2. Excision of the fibrous capsule returned both measures to pre-implantation levels (363mmHg and 5 % / mmHg x 10-2 respectively). ATM-FTIR comparison with unimplanted graft confirmed molecular stability of the polymer. Conclusions: Thi is the longest patency of any synthetic graft reported in a sheep model. This was due to anti-thrombogenicity with subsequent endothelialization and is despite compliance-reducing fibrous capsule. There was no biodegradation of the polymer. The model raises the possibility of spontaneous endothelialization of a synthetic graft in humans.