Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model

Paul J. Besseling, Wojciech Szymczyk, Martin Teraa, Raechel J. Toorop, Dan Jing Wu, Rob C.H. Driessen, Arturo M. Lichauco, Henk M. Janssen, Melanie van de Kaa, Krista den Ouden, Petra M. de Bree, Joost O. Fledderus, Carlijn V.C. Bouten, Gert J. de Borst, Patricia Y.W. Dankers, Marianne C. Verhaar (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Original languageEnglish
Article number2303888
JournalAdvanced Healthcare Materials
VolumeXX
Issue numberX
DOIs
Publication statusE-pub ahead of print - 7 Mar 2024

Funding

The authors thank K.R.D Vaessen, DVM, N.J.M. Attevelt, and H.M.L. de Bruin for their assistance with the animal studies. This study was supported by a grant from ZonMw within the LSH 2Treat programme, the Dutch Kidney Foundation [436001003 (InSiTeVx)], and the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). P.Y.W.D. is an inventor on patents that relate to the use of supramolecular interactions for advanced materials.

FundersFunder number
ZonMw
Nierstichting436001003
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024.003.013

    Keywords

    • AV shunt
    • biodegradable supramolecular material
    • biofunctionalization
    • goat model
    • in situ tissue engineering
    • vascular dialysis access

    Fingerprint

    Dive into the research topics of 'Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model'. Together they form a unique fingerprint.

    Cite this