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Regenerative and durable small-diameter graft as an arterial conduit
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2019
-
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(ε-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(ε-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.
- Subjects :
- Tunica media
Endothelium
Polyesters
Biocompatible Materials
02 engineering and technology
Fibrin
03 medical and health sciences
Mice
Suture (anatomy)
medicine.artery
medicine
Animals
Regeneration
030304 developmental biology
0303 health sciences
Multidisciplinary
biology
Tissue Engineering
Chemistry
Abdominal aorta
Correction
Arteries
021001 nanoscience & nanotechnology
medicine.disease
Tunica intima
medicine.anatomical_structure
PNAS Plus
Regional Blood Flow
biology.protein
Female
Vascular Grafting
Endothelium, Vascular
0210 nano-technology
Elastin
Calcification
Biomedical engineering
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 116
- Issue :
- 26
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....648bb023fa36fcae78e827d243c9d819