Heparinized Elastomeric Nanofibrillar Grafts: A Novel Approach for Mechanically Tunable, Cell-Supportive, and Thromboresistant Vascular Substitutes

The clinical success of vascular grafts relies on three main prerequisites: artery-tuned mechanics, cell-supportive microstructure, and a thromboresistant interface. Most current solutions address only a subset of this triad and equate mechanical matching with compliance alone, which can lead to disturbed hemodynamics, maladaptive mechanobiology, and adverse graft-host biochemical interactions that frequently culminate in clinical complications and graft failure. This study presents polyurethane-based heparin-functionalized elastomeric nanofibrillar grafts (H-ENGs) that integrate all three prerequisites while allowing multiparameter mechanical mimicry. To address the principal failure mode of early thrombosis, a small fraction of polyethyleneimine (PEI) is added to the ENG electrospinning solution to form P-ENGs, enabling one-step covalent heparin conjugation to form H-ENGs. The decoupled design of the ENG platform preserves the biomimetic microstructure and mechanics following PEI incorporation and heparinization, enabling adaptable, indication-specific optimization. In vitro, H-ENGs exhibit good cytocompatibility with minimal hemolysis, platelet adhesion, and whole blood clotting. Pilot porcine abdominal aorta interposition studies demonstrate feasibility: H-ENGs exhibit favorable surgical handling, intact suture-line integrity, and anastomotic hemostasis under dynamic flow, and retain artery-tuned mechanics and surface heparin at two weeks. While further testing is warranted, these results indicate that H-ENGs satisfy the three prerequisites for vascular graft clinical success.