Biofunctionalized Vascular Access Graft Improves Patency and Endothelialization in a Porcine Arteriovenous Model

TL;DR

A new vascular graft was developed that supports tissue regeneration and maintains mechanical strength in a pig model for hemodialysis.

Contribution

The study introduces a reinforced, biofunctionalized graft that enables in situ endothelialization and extracellular matrix remodeling in a large animal model.

Findings

The graft showed mechanical properties comparable to Gore-Tex PTFE, including kink resistance and burst pressure.

In vivo, the graft supported host cell infiltration, collagen deposition, and smooth muscle-like tissue formation.

Multiphoton imaging revealed greater collagen and elastin content in the graft compared to PTFE controls.

Abstract

Reliable vascular access remains a major clinical challenge for hemodialysis patients, as expanded polytetrafluoroethylene (PTFE) grafts exhibit poor patency and frequent complications driven by thrombosis and neointimal hyperplasia. Tissue-engineered vascular grafts offer a regenerative alternative but often lack the mechanical resilience required for high-flow arteriovenous (AV) environments. Here, we developed a reinforced, biofunctionalized coaxial electrospun graft comprising a poly(ε-caprolactone) mechanical core and a norbornene-functionalized poly(ethylene glycol) sheath incorporating pro-endothelialization cues. Circumferential PTFE rings were added to improve kink resistance. Grafts were implanted in a porcine AV configuration that recapitulates clinical hemodynamic conditions. Mechanical characterization included compliance, burst pressure, and kink resistance; host remodeling was assessed using histology, immunofluorescence, and multiphoton imaging at 4 weeks. Ring-reinforced electrospun grafts demonstrated a kink radius of 0.187 cm, compliance of 1.04 ± 0.29%/100 mmHg, and burst pressure of 1505 ± 565 mmHg, values all comparable to Gore-Tex PTFE and within industrial performance standards. In vivo, the electrospun grafts showed extensive host cell infiltration, collagen deposition, and formation of smooth muscle-like tissue, whereas PTFE controls remained largely acellular. Immunofluorescence confirmed intramural α-SMA+ and CD31+ cell populations, and multiphoton microscopy revealed significantly greater collagen and elastin content compared with PTFE (p < 0.05). Collectively, these findings demonstrate that the reinforced electrospun graft maintains mechanical integrity under physiological AV loading while supporting in situ endothelialization and extracellular matrix remodeling in a clinically relevant, large animal model. This work provides one of the first demonstrations of functional tissue regeneration within a fully synthetic, acellular scaffold in a porcine hemodialysis model and advances the translational development of durable, regenerative vascular access grafts that couple mechanical resilience with bioactive healing capacity.

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