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Kidney Week

Abstract: PO1333

Influence of CKD on In Situ Tissue Formation in Biodegradable Vascular Grafts

Session Information

  • Vascular Access
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 704 Dialysis: Vascular Access

Authors

  • Besseling, Paul J., University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands
  • Krebber, Merle M., University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands
  • Fledderus, Joost O., University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands
  • Teraa, Martin, University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands
  • Bouten, Carlijn V.c., Eindhoven University of Technology, Eindhoven, Noord-Brabant, Netherlands
  • Cox, Martijn, Xeltis bv, Eindhoven, Netherlands
  • Verhaar, Marianne C., University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands

Group or Team Name

  • InSiTeVx
Background

Vascular access is considered the Achilles' heel of hemodialysis, requiring frequent interventions to maintain patency. One proposed solution is a self-healing in situ tissue engineered vascular access graft. This requires the presence of a functional wound healing response capable of initiating tissue formation. However, it is unknown whether tissue formation is negatively affected by chronic kidney disease(CKD). In this study, we aim to investigate the effect of CKD on in situ tissue formation in vascular grafts in a rat model.

Methods

To mimic the effect of CKD in humans, a rat 5/6th nephrectomy model was created. Control animals underwent a sham operation. When CKD animals reached a threshold of 50mg/24h proteinuria an electrospun biodegradable vascular graft, made from supramolecular polymers, was implanted in the abdominal aorta. Explantation was performed at 2, 4, 8 and 12 weeks, to follow the different phases of wound healing and early tissue formation. Explants were examined for cell infiltration and proliferation, presence of immune, endothelial, smooth muscle cells, and extracellular matrix components.

Results

Cytometry of circulating immune cells shows an increase in monocytes(CD11b+) and macrophages(CD68+) in CKD animals. Histological analysis indicates that all implanted grafts contain infiltrated cells throughout the material with a non-significant increase over time in both groups. Both groups show a peak in proliferating cells at week 8, with virtually no proliferating cells at 12 weeks. Infiltrated macrophages (CD68+ & CD163+) show no significant difference between sham and CKD and peak at week 8 followed by a decline. Masson trichrome and Sirius red stains show an increase in ECM formation over time with no significant difference between groups. Mature vascular cells such as smooth muscle cells and endothelial cells are found from week 8 onward, indicating a shift from a proliferative phase to a remodeling stage.

Conclusion

The found difference in circulating immune cells this did not translate in a significant difference in tissue build up, cell type, ECM production, scaffold breakdown and patency between sham and CKD animals. Our data suggests that uremic conditions have a limited effect on tissue formation in creating in situ tissue engineered vascular grafts.

Funding

  • Government Support - Non-U.S.