Mechanically tuned vascular graft demonstrates rapid endothelialization and integration into the porcine iliac artery wall

Mechanical properties of vascular grafts likely play important roles in healing and tissue regeneration. Healthy arteries are compliant at low pressures but stiffen rapidly with increasing load, ensuring sufficient volumetric expansion without overstretching the vessel. Commercial synthetic vascular grafts are stiff and unable to expand under physiologic loads, which may result in altered hemodynamics, deleterious cellular responses, and compromised clinical performance. The goal of this study was to develop an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned nonlinear compliance and compare its healing responses to conventional expanded polytetrafluoroethylene (ePTFE) grafts in a porcine iliac artery model. Human and porcine iliac arteries were mechanically characterized, and an ENG with similar properties was created by utilizing residual strains within electrospun nanofibers. The ENG was tested for implantation suitability and implanted onto n = 5 domestic swine iliac arteries, with control ePTFE grafts implanted onto the contralateral iliac arteries. After two weeks in vivo, all iliac arteries and grafts remained patent with no signs of thrombosis or dilation. The mechanically tuned ENG implants exhibited a more confluent CD31-positive cell monolayer (1.53 ± 0.73 µm²/mm vs 0.52 ± 0.55 µm²/mm, p = 0.042) on the graft lumenal surface and a higher fraction of αSMA-positive cells (16.2 ± 8.6% vs 1.4 ± 0.7%, p = 0.018) within the graft wall than the ePTFE controls. Despite heavy cellular infiltration, the ENG retained its artery-like mechanical characteristics after two weeks in vivo. These short-term results demonstrate potential advantages of mechanically tuned biomimetic vascular grafts over standard ePTFE grafts. Statement of Significance: Off-the-shelf synthetic vascular grafts are often the only option available for treating advanced stages of vascular disease. Despite significant efforts devoted to improving their biochemical characteristics, synthetic peripheral arterial grafts continue to demonstrate poor clinical outcomes leading to costly reinterventions. Here, we hypothesized that a synthetic vascular graft with elastomeric mechanical properties tuned to a healthy peripheral artery promotes better healing responses than a synthetic stiff graft. To test this hypothesis, we developed an Elastomeric Nanofibrillar Graft (ENG) with artery-tuned mechanical properties and compared its performance to a commercial ePTFE graft in a preclinical porcine iliac artery model. Our results suggest that mechanically tuned ENGs can offer better healing responses, potentially leading to better clinical outcomes for peripheral arterial repairs.