Anti-thrombotic poly(AAm-co-NaAMPS)-xanthan hydrogel-expanded polytetrafluoroethylene (ePTFE) vascular grafts with enhanced endothelialization and hemocompatibility properties

Zhutong Li; Joshua Giarto; Jue Zhang; Neha Kulkarni; Esha Mahalingam; Will Klipstine; Lih-Sheng Turng

doi:10.1016/j.bioadv.2023.213625

Anti-thrombotic poly(AAm-co-NaAMPS)-xanthan hydrogel-expanded polytetrafluoroethylene (ePTFE) vascular grafts with enhanced endothelialization and hemocompatibility properties

Biomater Adv. 2023 Nov:154:213625. doi: 10.1016/j.bioadv.2023.213625. Epub 2023 Sep 14.

Authors

Zhutong Li¹, Joshua Giarto², Jue Zhang³, Neha Kulkarni², Esha Mahalingam⁴, Will Klipstine¹, Lih-Sheng Turng⁵

Affiliations

¹ Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
² Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
³ Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715, USA.
⁴ Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; College of Letters and Science, University of Wisconsin-Madison, Madison, WI, 53706, USA.
⁵ Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Mechanical Engineering, Chang Gung University, Tao-Yuan 33302, Taiwan. Electronic address: turng@engr.wisc.edu.

PMID: 37722163
PMCID: PMC10841274 (available on 2024-11-01)
DOI: 10.1016/j.bioadv.2023.213625

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death among all non-communicable diseases globally. Although expanded polytetrafluoroethylene (ePTFE) has been widely used for larger-diameter vascular graft transplantation, the persistent thrombus formation and intimal hyperplasia of small-diameter vascular grafts (SDVGs) made of ePTFE to treat severe CVDs remain the biggest challenges due to lack of biocompatibility and endothelium. In this study, bi-layered poly(acrylamide-co-2-Acrylamido-2-methyl-1-propanesulfonic acid sodium)-xanthan hydrogel-ePTFE (poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE) vascular grafts capable of promoting endothelialization and prohibiting thrombosis were synthesized and fabricated. While the external ePTFE layer of the vascular grafts provided the mechanical stability, the inner hydrogel layer offered much-needed cytocompatibility, hemocompatibility, and endothelialization functions. The interface morphology between the inner hydrogel layer and the outer ePTFE layer was observed by scanning electron microscope (SEM), which revealed that the hydrogel was well attached to the porous ePTFE through mechanical interlocking. Among all the hydrogel compositions tested with cell culture using human umbilical vein endothelial cells (HUVECs), the hydrogel with the molar ratio of 40:60 (NaAMPS/AAm) composition (i.e., Hydrogel 40:60) exhibited the best endothelialization function, as it produced the largest endothelialization area that was three times more than of that of plain ePTFE on day 14, maintained the highest average cell viability, and had the best cell morphology. Hydrogel 40:60 also showed excellent hemocompatibility, prolonged activated partial thromboplastin time (aPTT), and good mechanical properties. Overall, bi-layered poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE vascular grafts with the Hydrogel 40:60 composition could potentially solve the critical challenge of thrombus formation in vascular graft transplantation applications.

Keywords: Antithrombosis; Endothelialization; Hemocompatibility; Hydrogel; Vascular graft; ePTFE.

MeSH terms

Human Umbilical Vein Endothelial Cells
Humans
Hydrogels*
Polytetrafluoroethylene
Thrombosis*

Substances

xanthan gum
Hydrogels
Polytetrafluoroethylene

Grants and funding

U01 HL134655/HL/NHLBI NIH HHS/United States