Bioengineered cardiac patch constructed from multilayered mesenchymal stem cells for myocardial repair

Wei, Hao-Ji; Chen, Chun‐Hung; Lee, Wen-Yu; Chiu, I-Wen; Hwang, Shiaw-Min; Lin, Wei-Wen; Huang, Chieh‐Cheng; Yeh, Yi-Chun; Chang, Yen; Sung, Hsing‐Wen

doi:10.1016/j.biomaterials.2008.05.009

Cited by 133 publications

(78 citation statements)

References 29 publications

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“…Cardiac patches composed of sliced porous acellular bovine pericardium incorporated with multilayered MSC sheets were designed by Sung et al, and in vitro studies showed that MSCs tightly adhered to the fibronectin meshwork and redistributed throughout the scaffold. In vivo results showed that the cells together with neo-muscle fibers and neomicrovessels filled the pores of the scaffolds and the patch became well integrated within the host tissue [139]. Later, these researchers sandwiched ESC sheets into the sliced porous tissue scaffold and found that the mechanical properties of the engineered tissue were significantly increased [140].…”

Section: Cardiac Regenerationmentioning

confidence: 97%

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Prabhakaran

Venugopal

Ghasemi‐Mobarakeh

et al. 2011

Biomedical Applications of Polymeric Nanofibers

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Stem cells are a promising alternative for cell therapy applications because of their self-renewing capability and potential to differentiate into a wide range of specialized cell lineages, including osteoblasts, chondrocytes, cardiomyocytes, and neuronal cells. Different kinds of stem cells are considered for cell-based tissue engineering approaches, of which bone-marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived stem cells (ADSCs) and embryonic stem cells (ESCs) are frequently utilized for advancement of new tissue engineering strategies. Nanostructures created by natural, synthetic, or composite polymeric biomaterials provide artificial templates of the extracellular matrix (ECM). They possess a high surface area to volume ratio, are porous with good mechanical properties, are sufficient to serve as a biomimetic platform to attract stem cells, cause differentiation, and provide functioning of the tissues. Nanoscale features such as fibers, pits, and grooves modulate cell behavior and might even stimulate the differentiation of stem cells to specific lineages; for example, the nanotopographical cues combined with chemical cues influence the neuronal induction of MSCs, resulting in high microtubule-associated protein expressions. Scaffolds can also be impregnated with several ligands for adhesion of receptors to the cells, or with other regulatory molecules and growth M.P. Prabhakaran (*) and J. Venugopal E3-05-12, Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore e-mail: nnimpp@nus.edu.sg L. Ghasemi-Mobarakeh Islamic Azad University, Najafabad Branch, Isfahan, Iran D. Kai NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore G. Jin and S. Ramakrishna Department of Mechanical Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576, Singapore factors for designed cell behavior or controlled cell differentiations. Different polymeric blends or fibers incorporated with nanoparticles (such as hydroxyapatite) in aligned or custom-made patterns can induce specific differentiation of stem cells for bone, cartilage, cardiac, nerve, and skin tissue regeneration. In this review, we will discuss the current state of the art and future perspectives on stem cells and their differentiation on nanoengineered substrates for advanced tissue regeneration.

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Section: Cardiac Regenerationmentioning

confidence: 97%

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Prabhakaran

Venugopal

Ghasemi‐Mobarakeh

et al. 2011

Biomedical Applications of Polymeric Nanofibers

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“…Research has shown that composite materials composed of different matrices can stabilize heart tissue to decrease the consequences of a myocardial infarction, and such approaches include but are not limited to culturing patient tissue, 39,40 direct cell injection, 41,42 and biomaterial scaffolds. 43,44 Recently, the advent of advanced novel nanobiomaterials with improved properties capable of being used in several biomedical applications simultaneously has transformed the field of biomedical research and the world of cardiovascular biomaterials.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular application

Stout¹,

Yoo²,

Santiago-Miranda³

et al. 2012

IJN

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Background: Recent advances in nanotechnology (materials with at least one dimension between 1 nm and 100 nm) have led to the use of nanomaterials in numerous medical device applications. Recently, nanomaterials have been used to create innovative biomaterials for cardiovascular applications. Specifically, carbon nanofibers (CNF) embedded in poly(lacticco-glycolic-acid) (PLGA) have been shown to promote cardiomyocyte growth compared with conventional polymer substrates, but the mechanisms involved in such events remain unknown. The aim of this study was to determine the basic mechanism of cell growth on these novel nanocomposites. Methods: CNF were added to biodegradable PLGA (50:50 PGA:PLA weight ratio) to increase the conductivity, mechanical and cytocompatibility properties of pure PLGA. For this reason, different PLGA to CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt%) with different PLGA densities (0.1, 0.05, 0.025, and 0.0125 g/mL) were used, and their compatibility with cardiomyocytes was assessed. Results: Throughout all the cytocompatibility experiments, cardiomyocytes were viable and expressed important biomarkers, including cardiac troponin T, connexin-43, and alpha-sarcomeric actin (α-SCA). Adhesion and proliferation experiments indicated that a PLGA density of 0.025 g/mL with a PLGA to CNF ratio of 75:25 and 50:50 (wt%) promoted the best overall cell growth, ie, a 55% increase in cardiomyocyte density after 120 hours compared with pure PLGA and a 75% increase compared with the control at the same time point for 50:50 (wt%). The PLGA:CNF materials were conductive, and their conductivity increased as greater amounts of CNF were added to pure PLGA, from 0 S ⋅ m −1 for pure PLGA (100:0 wt%) to 5.5 × 10 −3 S ⋅ m −1 for pure CNF (0:100 wt%), as compared with natural heart tissue (ranging from 0.16 S ⋅ m −1 longitudinally to 0.005 S ⋅ m −1 transversely). Tensile tests showed that the addition of CNF increased the tensile strength to mimic that of natural heart tissue, ie, 0.15 MPa for 100% PLGA to 5.41 MPa for the 50:50 (PLGA to CNF [wt%:wt%]) ratio at 0.025 g/mL. Atomic force microscopy indicated that the addition of CNF to PLGA increased the material surface area from 10% (100:0 [PLGA to carbon nanofiber (wt%:wt%)]) to over 60% (50:50 [PLGA to carbon nanofibers (wt%:wt%)]). Lastly, the adsorption of specific proteins (fibronectin and vitronectin) showed significantly more adsorption for the 50:50 PLGA to CNF (wt%:wt%) ratio at 0.025 g/mL PLGA compared with pure PLGA, which may be why cardiomyocyte function increased on CNF-enriched composites. Conclusion:This study demonstrates that cardiomyocyte function was enhanced on 50:50 PLGA to CNF (wt%:wt%) composite ratios at 0.025 g/mL PLGA densities because they mimicked native heart tissue tensile strength/conductivity and increased the adsorption of proteins known to promote cardiomyocyte function.

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“…So far, mammalian stem cells have been employed in preclinical trials for the remedy of cardiovascular disorders. For example, mesenchymal stem cells were strategically piled up on a thin scaffold into a compact structure as therapy for myocardial weakness [1]. In addition, transplantation of neural stem cells into rat basal forebrain improved healing of the lesion in the central nervous system when brain-derived neurotrophic factor was injected into the lateral ventricle [2].…”

Section: Introductionmentioning

confidence: 99%

Capillary electrophoresis of bone marrow stromal cells with uptake of heparin‐functionalized poly(lactide‐co‐glycolide) nanoparticles during differentiation towards neurons

2010

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This study analyzes the varying electrophoretic mobility and zeta potential of bone marrow stromal cells (BMSCs) during their differentiation towards neurons. Electrophoresis of primary BMSCs and neuron growth factor (NGF)-induced neuron-like cells with the uptake of heparin-functionalized poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are also investigated. Immunofluorescent images revealed that a high concentration of NGF accelerated the differentiation of BMSCs into neurons. When the concentration of NGF increased, the absolute values of electrophoretic mobility and zeta potential of the differentiating BMSCs increased. In addition, a longer inductive period yielded higher charge of the differentiating BMSCs and a smaller uptake amount of heparin-functionalized PLGA NPs. However, an increase in the loading efficiency of heparin on PLGA NPs enhanced the uptake and reduced the electrical characteristics of the primary and differentiating BMSCs. Hence, a general rule is drawn that an increase in the uptake of heparin-functionalized PLGA NPs decreased the electrophoretic mobility and zeta potential of BMSCs during differentiation towards neurons.

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Bioengineered cardiac patch constructed from multilayered mesenchymal stem cells for myocardial repair

Cited by 133 publications

References 29 publications

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Stem Cells and Nanostructures for Advanced Tissue Regeneration

Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular application

Capillary electrophoresis of bone marrow stromal cells with uptake of heparin‐functionalized poly(lactide‐co‐glycolide) nanoparticles during differentiation towards neurons

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