Revisiting the tension-free paradigm: Axially prestretched elastomeric nanofibrillar grafts restore artery-like axial biomechanics in a preclinical model

This study developed Axially Prestretched Elastomeric Nanofibrillar Grafts (APENGs), synthetic small-diameter vascular grafts designed to restore the substantial axial prestretch normally present in healthy arteries. APENGs were fabricated from biomedical-grade polyurethane using ultrahigh-speed rotational electrospinning at 43,000 rpm, producing strongly circumferentially aligned nanofibers and pronounced mechanical anisotropy. The optimized grafts had an axial stiffness of 78.3 ± 30.7 N/m, approximately 4.2-fold lower than thickness-matched isotropic controls and comparable to native swine carotid arteries at 74.7 ± 11.7 N/m. They tolerated axial prestretch beyond 1.5 with low force while maintaining suture retention, low water permeability, and burst resistance above the 1000 mmHg testing limit. In vitro studies showed low hemolysis and good endothelial cytocompatibility, although platelet adhesion was greater than on ePTFE. In a bilateral swine carotid interposition model, prestretched APENGs were implanted at a nominal axial prestretch of approximately 1.5 and compared with contralateral non-prestretched controls. Prestretched grafts maintained elevated axial prestretch over two weeks, showed artery-like radial pulsatility and a trend toward reduced tortuosity, and remained mechanically compliant despite in vivo remodeling. Three of four prestretched grafts and all four controls remained patent at two weeks. Histology demonstrated early endothelialization, smooth muscle cell incorporation, limited neointimal thickening, and no significant differences in inflammatory response between groups. Overall, the study demonstrates that a synthetic vascular graft can be engineered to tolerate controlled artery-like axial prestretch, challenging conventional tension-free implantation and establishing axial prestretch as a potential design variable for vascular reconstruction and mechanobiology.