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

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.