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Tissue Eng Part A. 2018 Jan;24(1-2):135-144. doi: 10.1089/ten.TEA.2017.0044. Epub 2017 Jun 13.

Role of Bone Marrow Mononuclear Cell Seeding for Nanofiber Vascular Grafts.

Author information

1
1 Department of Cardiac Surgery, Johns Hopkins University , Baltimore, Maryland.
2
2 Tissue Engineering and Surgical Research, Nationwide Children's Hospital , Columbus, Ohio.
3
3 Nanofiber Solutions, Inc. , Columbus, Ohio.

Abstract

OBJECTIVE:

Electrospinning is a promising technology that provides biodegradable nanofiber scaffolds for cardiovascular tissue engineering. However, success with these materials has been limited, and the optimal combination of scaffold parameters for a tissue-engineered vascular graft (TEVG) remains elusive. The purpose of the present study is to evaluate the effect of bone marrow mononuclear cell (BM-MNC) seeding in electrospun scaffolds to support the rational design of optimized TEVGs.

METHODS:

Nanofiber scaffolds were fabricated from co-electrospinning a solution of polyglycolic acid and a solution of poly(ι-lactide-co-ɛ-caprolactone) and characterized with scanning electron microscopy. Platelet activation and cell seeding efficiency were assessed by ATP secretion and DNA assays, respectively. Cell-free and BM-MNC seeded scaffolds were implanted in C57BL/6 mice (n = 15/group) as infrarenal inferior vena cava (IVC) interposition conduits. Animals were followed with serial ultrasonography for 6 months, after which grafts were harvested for evaluation of patency and neotissue formation by histology and immunohistochemistry (n = 10/group) and PCR (n = 5/group) analyses.

RESULTS:

BM-MNC seeding of electrospun scaffolds prevented stenosis compared with unseeded scaffolds (seeded: 9/10 patent vs. unseeded: 1/10 patent, p = 0.0003). Seeded vascular grafts demonstrated concentric laminated smooth muscle cells, a confluent endothelial monolayer, and a collagen-rich extracellular matrix. Platelet-derived ATP, a marker of platelet activation, was significantly reduced after incubating thrombin-activated platelets in the presence of seeded scaffolds compared with unseeded scaffolds (p < 0.0001). In addition, reduced macrophage infiltration and a higher M2 macrophage percentage were observed in seeded grafts.

CONCLUSIONS:

The beneficial effects of BM-MNC seeding apply to electrospun TEVG scaffolds by attenuating stenosis through the regulation of platelet activation and inflammatory macrophage function, leading to well-organized neotissue formation. BM-MNC seeding is a valuable technique that can be used in the rational design of optimal TEVG scaffolds.

KEYWORDS:

biodegradable scaffold; bone marrow mononuclear cell (BM-MNC) seeding; electrospinning; nanofiber; stenosis; tissue-engineered vascular graft (TEVG)

PMID:
28486019
PMCID:
PMC5770093
DOI:
10.1089/ten.TEA.2017.0044
[Indexed for MEDLINE]
Free PMC Article

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