Regenerative and durable small-diameter graft as an arterial conduit

Morgan B. Elliott, Brian Ginn, Takuma Fukunishi, Djahida Bedja, Abhilash Suresh, Theresa Chen, Takahiro Inoue, Harry C. Dietz, Lakshmi Santhanam, Hai Quan Mao, Narutoshi Hibino, Sharon Gerecht

Research output: Contribution to journalArticlepeer-review

Abstract

Despite significant research efforts, clinical practice for arterial bypass surgery has been stagnant, and engineered grafts continue to face postimplantation challenges. Here, we describe the development and application of a durable small-diameter vascular graft with tailored regenerative capacity. We fabricated small-diameter vascular grafts by electrospinning fibrin tubes and poly(e-caprolactone) fibrous sheaths, which improved suture retention strength and enabled long-term survival. Using surface topography in a hollow fibrin microfiber tube, we enable immediate, controlled perfusion and formation of a confluent endothelium within 3–4 days in vitro with human endothelial colony-forming cells, but a stable endothelium is noticeable at 4 weeks in vivo. Implantation of acellular or endothelialized fibrin grafts with an external ultrathin poly(e-caprolactone) sheath as an interposition graft in the abdominal aorta of a severe combined immunodeficient Beige mouse model supports normal blood flow and vessel patency for 24 weeks. Mechanical properties of the implanted grafts closely approximate the native abdominal aorta properties after just 1 week in vivo. Fibrin mediated cellular remodeling, stable tunica intima and media formation, and abundant matrix deposition with organized collagen layers and wavy elastin lamellae. Endothelialized grafts evidenced controlled healthy remodeling with delayed and reduced macrophage infiltration alongside neo vasa vasorum-like structure formation, reduced calcification, and accelerated tunica media formation. Our studies establish a small-diameter graft that is fabricated in less than 1 week, mediates neotissue formation and incorporation into the native tissue, and matches the native vessel size and mechanical properties, overcoming main challenges in arterial bypass surgery.

Original languageEnglish (US)
Pages (from-to)12710-12719
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number26
DOIs
StatePublished - 2019

Keywords

  • Electrospinning
  • Endothelial colony-forming cells
  • Hydrogel
  • Infrarenal abdominal aorta mouse model
  • Small-diameter vascular graft

ASJC Scopus subject areas

  • General

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