Fabrication of Blood-Derived Elastogenic Vascular Grafts Using Electrospun Fibrinogen and Polycaprolactone Composite Scaffolds for Pediatric Applications

Ian Woods, Alexander Black, Eleanor J Molloy, Stefan Jockenhoevel, Thomas C Flanagan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

The development of tissue-engineered vascular grafts (TEVGs) for pediatric applications must consider unique factors associated with this patient cohort. While the increased elastogenic potential of neonatal cells offers an opportunity to overcome the long-standing challenge of in vitro elastogenesis, neonatal patients have a lower tolerance for autologous tissue harvest and require grafts that exhibit growth potential. The purpose of this study was to apply a multi-pronged strategy to promote elastogenesis in conjunction with umbilical cord-derived materials in the production of a functional pediatric TEVG. An initial proof-of-concept study was performed to extract fibrinogen from human umbilical cord blood samples and, through electrospinning, to produce a nanofibrous fibrinogen scaffold. This scaffold was seeded with human umbilical cord artery-derived smooth muscle cells (hUASMCs) and neotissue formation within the scaffold was examined using immunofluorescence microscopy. Subsequently, a polycaprolactone (PCL)-reinforced porcine blood-derived fibrinogen scaffold (isolated using the same protocol as cord blood fibrinogen) was used to develop a rolled-sheet graft which employed topographical and biochemical guidance cues to promote elastogenesis and cellular orientation. This approach resulted in a TEVG with robust mechanical properties, and biomimetic arrangement of extracellular matrix (ECM) with rich expression of elastic-fiber related proteins (EFRPs). The results of this study hold promise for further development of pediatric TEVGs and the exploration of the effects of scaffold micro- and nanostructure on vascular cell function and ECM production.

Original languageEnglish
Pages (from-to)1281-1295
Number of pages15
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume14
Issue number9
Early online date12 Jul 2020
DOIs
Publication statusPublished - Sep 2020

Keywords

  • ARTERY
  • CELL INFILTRATION
  • DIAMETER
  • MECHANICAL-PROPERTIES
  • MORTALITY
  • TISSUE
  • UMBILICAL-CORD BLOOD
  • VEIN
  • congenital heart defect
  • elastin
  • electrospinning
  • fibrinogen
  • nanofibre
  • vascular graft

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