The heart does not regenerate new functional tissue when myocardium
dies following coronary artery occlusion, or is defective. Ventricular restoration
involves excising the infarct and replacing it with a cardiac patch to restore the heart
to a more efficient condition. The goal of this study was to design and develop a
myocardial patch to replace myocardial infarctions. A basic design was developed
that is composed of 3D microfibrous mats that house mesenchymal stem cells
(MSCs) from umbilical cord matrix (Wharton&rsquo / s Jelly) aligned parallel to each other,
and biodegradable macroporous tubings to supply growth media into the structure.
Poly(glycerol sebacate) (PGS) prepolimer was synthesized and blended
with P(L-D,L)LA and/or PHBV, to produce aligned microfiber (dia 1.16 - 1.37 & / #956 / m)
mats and macroporous tubings. Hydrophilicity and softness of the polymer blends
were found to be improved as a result of PGS introduction. The Wharton&rsquo / s Jelly
(WJ) MSCs were characterized by determination of their cell surface antigens with
flow cytometry and by differentiating them into cells of mesodermal lineage
(osteoblasts, adipocytes, chondrocytes). Cardiomyogenic differentiation potential of
WJ MSCs in presence of differentiation factors was studied with RT-PCR and immunocytochemistry. WJ MSCs expressed cardiomyogenic transcription factors
even in their undifferentiated state. Expression of a ventricular sarcomeric protein
was observed upon differentiation. The electrospun, aligned microfibrous mats of
PHBV-P(L-D,L)LA-PGS blends allowed penetration of WJ MSCs and improved
cell proliferation. To obtain the 3D myocardial graft, the WJ MSCs were seeded on
the mats, which were then wrapped around macroporous tubings. The 3D construct
(4 mm x 3.5 cm x 2 mm) was incubated in a bioreactor and maintained the uniform
distribution of aligned cells for 2 weeks. The positive effect of nutrient flow within
the 3D structure was significant.
This study represents an important step towards obtaining a thick,
autologous myocardial patch, with structure similar to native tissue and capability to
grow, for ventricular restoration.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/3/12610315/index.pdf |
| Date | 01 December 2008 |
| Creators | Kenar, Halime |
| Contributors | Hasirci, Vasif |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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