Spelling suggestions: "subject:"cardiac tissue engineering"" "subject:"ardiac tissue engineering""
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3d Patterned Cardiac Tissue Construct Formation Using Biodegradable MaterialsKenar, Halime 01 December 2008 (has links) (PDF)
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.
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The Development of Elastomeric Biodegradable Polyurethane Scaffolds for Cardiac Tissue EngineeringParrag, Ian 01 September 2010 (has links)
In this work, a new polyurethane (PU) chain extender was developed to incorporate a Glycine-Leucine (Gly-Leu) dipeptide, the cleavage site of several matrix metalloproteinases. PUs were synthesized with either the Gly-Leu-based chain extender (Gly-Leu PU) or a phenylalanine-based chain extender (Phe PU). Both PUs had high molecular weight averages (Mw > 125,000 g/mol) and were phase segregated, semi-crystalline polymers (Tm ~ 42°C) with a low soft segment glass transition temperature (Tg < -50°C). Uniaxial tensile testing of PU films revealed that the polymers could withstand high ultimate tensile strengths (~ 8-13 MPa) and were flexible with breaking strains of ~ 870-910% but the two PUs exhibited a significant difference in mechanical properties.
The Phe and Gly-Leu PUs were electrospun into porous scaffolds for degradation and cell-based studies. Fibrous Phe and Gly-Leu PU scaffolds were formed with randomly organized fibers and an average fiber diameter of approximately 3.6 µm. In addition, the Phe PU was electrospun into scaffolds of varying architecture to investigate how fiber alignment affects the orientation response of cardiac cells. To achieve this, the Phe PU was electrospun into aligned and unaligned scaffolds and the physical, thermal, and mechanical properties of the scaffolds were investigated.
The degradation of the Phe and Gly-Leu PU scaffolds was investigated in the presence of active MMP-1, active MMP-9, and a buffer solution over 28 days to test MMP-mediated and passive hydrolysis of the PUs. Mass loss and structural assessment suggested that neither PU experienced significant hydrolysis to observe degradation over the course of the experiment.
In cell-based studies, Phe and Gly-Leu PU scaffolds successfully supported a high density of viable and adherent mouse embryonic fibroblasts (MEFs) out to at least 28 days. Culturing murine embryonic stem cell-derived cardiomyocytes (mESCDCs) alone and with MEFs on aligned and unaligned Phe PU scaffolds revealed both architectures supported adherent and functionally contractile cells. Importantly, fiber alignment and coculture with MEFs improved the organization and differentiation of mESCDCs suggesting these two parameters are important for developing engineered myocardial constructs using mESCDCs and PU scaffolds.
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The Development of Elastomeric Biodegradable Polyurethane Scaffolds for Cardiac Tissue EngineeringParrag, Ian 01 September 2010 (has links)
In this work, a new polyurethane (PU) chain extender was developed to incorporate a Glycine-Leucine (Gly-Leu) dipeptide, the cleavage site of several matrix metalloproteinases. PUs were synthesized with either the Gly-Leu-based chain extender (Gly-Leu PU) or a phenylalanine-based chain extender (Phe PU). Both PUs had high molecular weight averages (Mw > 125,000 g/mol) and were phase segregated, semi-crystalline polymers (Tm ~ 42°C) with a low soft segment glass transition temperature (Tg < -50°C). Uniaxial tensile testing of PU films revealed that the polymers could withstand high ultimate tensile strengths (~ 8-13 MPa) and were flexible with breaking strains of ~ 870-910% but the two PUs exhibited a significant difference in mechanical properties.
The Phe and Gly-Leu PUs were electrospun into porous scaffolds for degradation and cell-based studies. Fibrous Phe and Gly-Leu PU scaffolds were formed with randomly organized fibers and an average fiber diameter of approximately 3.6 µm. In addition, the Phe PU was electrospun into scaffolds of varying architecture to investigate how fiber alignment affects the orientation response of cardiac cells. To achieve this, the Phe PU was electrospun into aligned and unaligned scaffolds and the physical, thermal, and mechanical properties of the scaffolds were investigated.
The degradation of the Phe and Gly-Leu PU scaffolds was investigated in the presence of active MMP-1, active MMP-9, and a buffer solution over 28 days to test MMP-mediated and passive hydrolysis of the PUs. Mass loss and structural assessment suggested that neither PU experienced significant hydrolysis to observe degradation over the course of the experiment.
In cell-based studies, Phe and Gly-Leu PU scaffolds successfully supported a high density of viable and adherent mouse embryonic fibroblasts (MEFs) out to at least 28 days. Culturing murine embryonic stem cell-derived cardiomyocytes (mESCDCs) alone and with MEFs on aligned and unaligned Phe PU scaffolds revealed both architectures supported adherent and functionally contractile cells. Importantly, fiber alignment and coculture with MEFs improved the organization and differentiation of mESCDCs suggesting these two parameters are important for developing engineered myocardial constructs using mESCDCs and PU scaffolds.
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Développement d’un système d’imagerie haute vitesse pour la surveillance en continue de cultures cardiaquesBelzil, Antoine 12 1900 (has links)
No description available.
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Cardiac Repair Using A Decellularized Xenogeneic Extracellular MatrixShah, Mickey January 2018 (has links)
No description available.
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Functional Tissue Engineering of Myocardium Through Cell Tri-cultureIyer, Rohin 22 August 2012 (has links)
Cardiac tissue engineering promises to create therapeutic tissue replacements for repair of diseased native myocardium. The main goals of this thesis were four-fold: 1) to evaluate cardiac tissues engineered using multiple cell types including endothelial cells (EC), fibroblasts (FB), and cardiomyocytes (CM); 2) to spatiotemporally track cells in organoids and optimize their seeding percentages for improved function; 3) to enhance vascular cord formation through sequential versus simultaneous seeding of ECs and FBs; and 4) to perform mechanistic studies to elucidate the role of soluble factors in cell-cell communication. Microscale templates fabricated from photocrosslinkable poly(ethylene glycol) diacrylate (PEG-DA) were used for all studies for rapid screening. When ECs and FBs were precultured for two days prior to seeding enriched CMs, cells self-assembled into three-dimensional, beating organoids, compared to simultaneously tricultured EC/ FB / CM which formed non-contractile clusters. Fluorescent dyes were used to label and track each cell type for up to 4 days, demonstrating an even distribution of cells within precultured organoids versus EC clustering in simultaneous triculture. When ECs were seeded first, followed by FBs 24 hours later and CMs 48 hours later, vascular-like cords formed that persisted with time in a seeding density-dependent manner. Vascular endothelial growth factor (VEGF) signaling was quantified, showing higher endogenous VEGF secretion rates in sequential preculture (16.6 ng/mL/hr) compared to undetectable VEGF secretion in simultaneous triculture. Blocking of endogenous VEGF signaling through addition of VEGF antibody / VEGFR2 inhibitor resulted in a significant decrease in mRNA and protein expression of the key cardiac gap junctional marker connexin-43. These findings provide a foundation for future work into the mechanisms governing functional cardiac tissue engineering performance and may aid in the development of novel therapies for heart failure based on growth factor signaling and engineering of vascularized, clinically relevant cardiac tissue patches.
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Functional Tissue Engineering of Myocardium Through Cell Tri-cultureIyer, Rohin 22 August 2012 (has links)
Cardiac tissue engineering promises to create therapeutic tissue replacements for repair of diseased native myocardium. The main goals of this thesis were four-fold: 1) to evaluate cardiac tissues engineered using multiple cell types including endothelial cells (EC), fibroblasts (FB), and cardiomyocytes (CM); 2) to spatiotemporally track cells in organoids and optimize their seeding percentages for improved function; 3) to enhance vascular cord formation through sequential versus simultaneous seeding of ECs and FBs; and 4) to perform mechanistic studies to elucidate the role of soluble factors in cell-cell communication. Microscale templates fabricated from photocrosslinkable poly(ethylene glycol) diacrylate (PEG-DA) were used for all studies for rapid screening. When ECs and FBs were precultured for two days prior to seeding enriched CMs, cells self-assembled into three-dimensional, beating organoids, compared to simultaneously tricultured EC/ FB / CM which formed non-contractile clusters. Fluorescent dyes were used to label and track each cell type for up to 4 days, demonstrating an even distribution of cells within precultured organoids versus EC clustering in simultaneous triculture. When ECs were seeded first, followed by FBs 24 hours later and CMs 48 hours later, vascular-like cords formed that persisted with time in a seeding density-dependent manner. Vascular endothelial growth factor (VEGF) signaling was quantified, showing higher endogenous VEGF secretion rates in sequential preculture (16.6 ng/mL/hr) compared to undetectable VEGF secretion in simultaneous triculture. Blocking of endogenous VEGF signaling through addition of VEGF antibody / VEGFR2 inhibitor resulted in a significant decrease in mRNA and protein expression of the key cardiac gap junctional marker connexin-43. These findings provide a foundation for future work into the mechanisms governing functional cardiac tissue engineering performance and may aid in the development of novel therapies for heart failure based on growth factor signaling and engineering of vascularized, clinically relevant cardiac tissue patches.
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Development of a novel technology to engineer heart muscle for contractile and paracrine support in heart failureSoong, Poh Loong 23 October 2012 (has links)
The human heart has poor endogenous regeneration. If myocytes are lost due
to injury, the myocardium is unable to restore its myocyte content and instead
undergoes compensatory hypertrophy and remodeling. Cardiac tissue
engineering aims to recreate and provide functional myocardium that replaces
the injured myocardium. In this study, human engineered heart muscle (EHM)
from cardiomyogenically differentiated human embryonic stem cells was
generated. EHMs consisted of elongated, anisotropically organized
cardiomyocyte bundles and responded “physiologically” to increasing calcium
concentrations. To generate large myocardium capable of encompassing the
ventricles, a novel process to systematically upscale the dimensions of
engineered myocardium to a humanized Biological Ventricular Assisted Device
(hBioVAD) was introduced. The hBioVADs formed a “pouch-like” myocardium at
rabbit heart dimensions and were beating spontaneously. Further enhancement
by biomimetic pulsatile loading generated “more mature” myocardium.
Additional paracrine functionality was integrated by generating insulin-like
growth factor-1 (IGF-1) secreting fibroblasts for tissue engineering applications.
IGF-1 release induced higher levels of Akt phosphorylation and hypertrophy in
cardiomyocytes resulting in increased force generation of EHM. Finally,
feasibility of “paraBioVAD” (IGF-1 cell line and cardiomyocytes) implantation
was demonstrated in a healthy rat model. Histological observations
demonstrated engraftment on the heart and the presence of vascular structures.
In conclusion, a humanized “paraBioVAD” technology for mechanic and
paracrine heart support was developed. Future studies will assess its
therapeutic utility in heart failure
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