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

Healthy arteries function under substantial axial prestretch (AP), the ratio of in vivo to unloaded ex vivo length. Loss of AP promotes tortuosity and disturbed hemodynamics associated with vascular pathology, yet artery-like AP has not been incorporated in vascular reconstructions, because conventional substitutes are axially stiff and cannot safely sustain physiological AP. Here, we present Axially Prestretched Elastomeric Nanofibrillar Grafts (APENGs), fabricated by ultrahigh-speed (43,000 rpm) rotational collector electrospinning of biomedical-grade polyurethane. APENGs matched native arterial axial stiffness and tolerated elastomeric elongation beyond AP = 1.5 without failure, excessive force generation, or plastic deformation, while maintaining adequate suture retention, permeability, and burst strength. In vitro, APENGs supported endothelial cytocompatibility and low hemolysis. In a bilateral swine carotid interposition model (8 grafts, two-week follow-up), experimental APENGs (nominal AP ≈ 1.5) achieved and retained elevated prestretch and reduced tortuosity relative to contralateral controls (nominal AP ≈ 1.0). Patency was 75% (prestretched) versus 100% (controls). Histology showed rapid mid-graft endothelialization, early smooth muscle ingrowth, and limited neointimal thickening near anastomoses. This study demonstrates the first synthetic graft implanted with controlled, artery-like AP, challenging the tension-free anastomosis paradigm and positioning AP as a vascular graft design lever to restore native artery biomechanics and mechanobiology. STATEMENT OF SIGNIFICANCE: AP is an essential homeostatic state of healthy arteries that supports arterial biomechanics and mechanobiology. Reduction in AP is associated with tortuosity, disturbed flow, and maladaptive vascular responses, yet its mechanisms remain understudied. AP is absent from current grafts, which are too stiff to safely sustain physiological elongation, forcing tension-free implantation and leaving axial biomechanics unrestored. Here, we present APENGs, manufactured by ultrahigh-speed rotational electrospinning to achieve artery-like low axial stiffness. In a swine carotid interposition model, APENGs with controlled physiological AP demonstrated surgical feasibility, reduced tortuosity, biomimetic pulsatility, and early endothelialization. These findings challenge the tension-free paradigm and establish APENGs as a platform for restoring and studying AP-regulated vascular biomechanics and remodeling.