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Vascular transplantation with dual-biofunctional ePTFE vascular grafts in a porcine model
Zheng Xing1, Shuting Wu2, Chen Zhao3
1Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, P. R. China. haifengliu@buaa.edu.cn.
Insights
Surface modification of expanded polytetrafluoroethylene (ePTFE) vascular grafts with bivalirudin (BVLD) and REDV peptides improved blood vessel function. This enhanced ePTFE graft shows promise for treating cardiovascular disease (CVD).
Area of Science:
- Biomaterials Science
- Cardiovascular Surgery
- Regenerative Medicine
Background:
- Cardiovascular disease (CVD) presents a global health challenge, with a critical need for effective vascular grafts.
- Expanded polytetrafluoroethylene (ePTFE) grafts have limitations, particularly low long-term patency in small-diameter applications.
- Surface modification of ePTFE is essential to improve its performance and address clinical needs.
Purpose of the Study:
- To enhance the bioactivity and anti-thrombotic properties of ePTFE vascular grafts.
- To investigate the co-modification of ePTFE with polydopamine (PDA), bivalirudin (BVLD), and REDV peptides.
- To evaluate the efficacy of modified ePTFE grafts in a preclinical animal model.
Main Methods:
- Surface modification of ePTFE using polydopamine (PDA) for improved hydrophilicity and immobilization.
- Co-modification with bivalirudin (BVLD), a direct thrombin inhibitor, to impart anti-thrombotic properties.
- Incorporation of REDV peptides derived from extracellular matrix proteins to enhance bioactivity.
- In vitro evaluation of endothelial cell proliferation and in vivo assessment using a porcine carotid artery replacement model.
Main Results:
- The BVLD/REDV co-modified ePTFE grafts demonstrated improved hydrophilicity, hemocompatibility, and bioactivity.
- In vitro assays confirmed enhanced endothelial cell proliferation on the modified grafts.
- The porcine carotid artery replacement model showed a satisfactory patency rate of 66.7% at 12 weeks.
- High endothelial cell coverage ratio (70%) was observed at 12 weeks post-implantation.
Conclusions:
- Co-modification of ePTFE with BVLD and REDV peptides offers a promising strategy for developing multi-biofunctional vascular grafts.
- These enhanced ePTFE grafts show potential to address the unmet clinical need for improved small-diameter vascular replacements in CVD treatment.
- The developed graft holds potential for clinical translation, offering a more effective solution for cardiovascular reconstructive surgery.
Abstract:
Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft in vitro. Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.
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