A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig

John Joseph,Raimondo Ascione,Helna Mary Baby,Vito Domenico Bruno,Alexander Ward,Nadiah Sulaiman,Praveen Kerala Varma,Shantikumar V Nair,Deepthy Menon,Thomas W Johnson,Rajesh Jose,Sarah Jane George

doi:10.1186/s12951-022-01268-1

Abstract

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.Graphical

Highlights

Worldwide > 220 million patients are at risk of stroke, myocardial infarction, lower limb gangrene, and amputation due to severe atherosclerosis, a disease mainly affecting arteries with < 6 mm diameter [1]
In‐vitro testing of leakage, physical properties, and biocompatibility of the single layered NanoGraft Flexible and kink-resistant nanotextile conduits of 4 mm diameter were developed from polymeric nanofibrous yarns of electrospun poly(L-lactic acid) (PLLA) using a modified weaving system as described earlier [18], see Fig. 1a–c
This interwoven structure resulted in a significantly high burst pressure compared to the control expanded polytetrafluoroethylene grafts (ePTFE) graft (p < 0.0001) (Fig. 1d)

Summary

Introduction

Worldwide > 220 million patients are at risk of stroke, myocardial infarction, lower limb gangrene, and amputation due to severe atherosclerosis, a disease mainly affecting arteries with < 6 mm diameter [1]. Available synthetic ePTFE and polyethylene terephthalate (PET) grafts made from non-degradable materials feature lower patency rates of < 50% at 1-year due to poor endothelialisation, marked intimal thickening, and acute thrombosis [12] This is triggered by the low flow through the small cross-sectional area and high turbulence at the anastomotic sites. Different strategies of engineering small vascular grafts have utilized biodegradable polymers, surface modification techniques, tissue engineering, and decellularization of xenografts [15, 16] None of these approaches have proven success.

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Discussion

Conclusion