Engineering Conductive Vascular Grafts with S-PEDOT for Next Generation Vascular Prostheses

Introduction: Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, often necessitating the replacement of damaged blood vessels with prosthetic vascular grafts. Conventional vascular grafts suffer from limitations such as poor long-term patency and the inability to provide real-time information about graft performance. This project aims to develop a novel generation of vascular grafts that are not only biocompatible but also electrically conductive. These bioelectronic vascular grafts will pave the way for smart vascular prostheses with built-in bio-sensing capabilities, addressing the shortcomings of current vascular graft technologies.

Materials and

Methods: Commercially available collagen sponge materials and decellularized Sprague-Dawley rat aortas were hydrated in PBS. Highly soluble, self-doped conductive polymer sulfonated poly(3,4-ethylenedioxythiophene) (S-PEDOT) was synthesized via oxidative polymerization before or during incubation with sponges and aortas at varying concentrations (0.5, 1, or 10% S-EDOT). After polymerization and incubation, all materials underwent a 24-hour leaching step and sonication at room temperature to remove unbound material. S-PEDOT loading efficiency was calculated by measuring the change in dry weight of each sponge after the polymerization had occurred. Conductivity of the modified sponges and aortas were measured via 4-point probe. Extracellular matrix structure in the aorta samples was imaged with SEM.

To evaluate in vitro biocompatibility of S-PEDOT incorporation, human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (HAoSMCs) were cultured on collagen sponges modified with S-PEDOT. Live/dead staining and immunocytochemistry were performed after 24 hours. To assess biocompatibility in vivo, S-PEDOT-incorporated aorta sections were implanted subcutaneously in Sprague-Dawley rats for two weeks. H&E, Masson’s trichrome, and immunofluorescence staining were performed to assess inflammation.

Results, Conclusions, and Discussions: The final molecular structure of S-PEDOT demonstrates a sulfonate group for water solubility (blue dashed box) and a methyl group for improved stability (green solid box) (1A). The additional methyl group can be observed by NMR (1B). Modified collagen sponges turn from white to black, indicative of high levels of S-PEDOT loading (1C – 1D). S-PEDOT sponges demonstrate higher conductivity than collagen sponges alone (1E). S-PEDOT-modified decellularized aortas demonstrated thorough monomer penetration and subsequent polymerization as seen by the change in color through (dashed circle) and along the length of (solid box) the vascular wall (1F). S-PEDOT modification leaves collagen fibers intact as seen with SEM (1G), and aortas also demonstrate improved conductivity when S-PEDOT polymerization is performed (1H).

S-PEDOT shows no cytotoxicity in HUVECs or HAoSMCs with live/dead staining (2A), and cells can spread on S-PEDOT modified sponges (2B). No evidence of infection, seroma, or delayed wound healing was observed in subcutaneous implantation studies (3A – 3B), though macrophage infiltration (CD68+) was noted to be qualitatively elevated around the decellularized vessels (αSMA-) (3C).

In conclusion, conductive vascular grafts can be easily generated by modifying decellularized aortas with S-PEDOT via in situ polymerization. Both collagen sponges and decellularized aortas demonstrate significant increases in conductivity after S-PEDOT polymerization. S-PEDOT-modified extracellular matrix materials demonstrate biocompatibility both in vitro and in vivo, further supporting the use of S-PEDOT modification for electrically conductive vascular grafts. Future directions for the work include implanting S-PEDOT-modified decellularized aortas in a rat abdominal aortic interposition model to evaluate graft functionality with physiological hemodynamics.

Acknowledgements (Optional): TKB is funded by American Heart Association Predoctoral Fellowship (24PRE1199686) and RD is funded by Center for Advanced Regenerative Engineering RE-Training Program (NIH T32-EB031527). Scanning Electron Microscopy (Hitachi S-4800) performed at the EPIC facility of Northwestern University’s NUANCE Center, supported by NSF ECCS-2025633, the IIN, and NSF DMR-2308691. Confocal Microscopy (Nikon AXR) imaging was performed at the Northwestern University Center for Advanced Microscopy, supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center.