A Comparative Study of an Anti-Thrombotic Small-Diameter Vascular Graft with Commercially Available e-PTFE Graft in a Porcine Carotid Model

Abstract

Background: We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO + 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. Methods: A total of 10 pigs (weight: 25–35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO + 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). Results: No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO + 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO + 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO + 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. Conclusion: The PCL/PDO + 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

Rapid remodeling observed at mid-term in-vivo study of a smart reinforced acellular vascular graft implanted on a rat model

“…Vascular grafts were fabricated in accordance with our previously described procedure, with slight modifications [ 14 ]. Briefly, PCL was dissolved in a 5:1 ratio of chloroform and ethyl alcohol at 10% (w/v) concentration; PDO pellets were placed in HFIP at 8% (w/v) concentration in a separate vial.…”

Strategies to counteract adverse remodeling of vascular graft: A 3D view of current graft innovations

“…Regardless of graft materials or fabrication methods, heparinized grafts, including ePTFE grafts ( Samson et al, 2016 ; Freeman et al, 2018 ), electrospun grafts ( Qiu et al, 2017 ; Xu et al, 2018 ; Shi et al, 2019b ; Matsuzaki et al, 2021 ; Zhu et al, 2021 ), and decelluarized grafts ( Kong et al, 2019 ), all outperformed those without heparin in terms of graft patency, showing critical roles of heparin in the thromboresistance and in situ endothelialization. Besides heparin, anticoagulation methods include the incorporation of anti-thrombotic drugs ( Lee et al, 2022 ), hyaluronic acid ( Dimitrievska et al, 2020 ) or more sophisticated ECM secreted by thrombospondin-2 knockout cells on decellularized aorta grafts ( Kristofik et al, 2017 ).…”

Investigation on the Temperature Distribution Uniformity of an Extrusion-Based 3D Print Head and Its Temperature Control Strategy

“…Because the chemical structure of the molecule chains of the thermoplastic polymers is prone to be destroyed under high temperature, the maximum value of the controlled temperature should be limited. Generally, the printing process for the thermoplastic polymers which are employed in the fabrication of biocompatible scaffolds can be conducted at a temperature below 180 °C [ 22 , 23 , 24 ], hence, the maximum heating temperature in the simulation was set to 180 °C.…”

“…The potential of the fabricated scaffolds for tissue engineering was demonstrated by analyses of enzymatic degradation and antibacterial activity. Lee et al [ 23 ] fabricated a vascular graft with melts of PCL and PDO. They adopted an extrusion-based 3D printing device to deposit the PCL filaments onto a prepared nanofibrous PCL/PDO scaffold at 90 °C.…”