Prolonged In Vivo Performance of Electrospun PCL-Based Vascular Grafts in a Large Animal Model: Influence of Material Design and Systemic Drug Support

TL;DR

This study explores how material design and drug support affect the long-term success of biodegradable vascular grafts in large animals.

Contribution

The study introduces bilayer electrospun vascular grafts with specific fiber orientations and evaluates their performance with systemic drug support in a porcine model.

Findings

PCL_PCL grafts showed longer patency, especially with enoxaparin treatment, lasting up to 90 days.

PCLPLA_PLCL grafts had higher radial strength but lower compliance and early failure due to delamination.

Inflammation, fibrin deposition, and fibrosis were the main causes of graft occlusion.

Abstract

The development of biodegradable vascular grafts that
replicate
the structural and functional characteristics of native vessels remains
a critical challenge in regenerative medicine. Although in
vitro studies have demonstrated promising outcomes, the long-term
success of electrospun vascular grafts in large animal models has
been limited due to mechanical incompatibility, insufficient interfacial
adhesion, and thrombotic issues. In this study, bilayer vascular grafts
composed of polycaprolactone (PCL), polylactic acid (PLA), and poly­(l-lactide-co-caprolactone) (PLCL) were developed
and fabricated using the electrospinning technique, and after testing
biological and mechanical performance, they were implanted and evaluated
in a porcine carotid artery model. Two bilayer configurations were
designed, namely, PCL_PCL and PCLPLA_PLCL, consisting of random fiber
distribution in inner layers and radial fiber orientation in outer
layers to mimic native arteries. Mechanical test results revealed
that developed grafts provided adequate performance in terms of tensile
strength, burst pressure, compliance, and suture retention strength
when compared with native carotid arteries. PCLPLA_PLCL grafts exhibited
higher radial strength due to the presence of PLA but showed lower
compliance. In vivo results indicated early graft
failure in PCLPLA_PLCL samples, which might be associated with delamination
at the interface. In contrast, PCL_PCL grafts achieved longer patency,
particularly in animals receiving enoxaparin via intradermal injection,
with one graft remaining partially patent for up to 90 days, a finding
rarely reported in porcine studies. Histological evaluation revealed
that inflammation, fibrin deposition, and fibrotic tissue formation
were the primary causes of graft occlusion. Overall, the results demonstrated
that material selection and pharmacological management play decisive
roles in the long-term performance of small-diameter vascular grafts.
Electrospun PCL-based bilayer constructs appear to hold significant
potential for future clinical applications.

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