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JCDD
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Cardiovascular Tissue Engineering
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Cardiovascular Tissue Engineering

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425). This special issue belongs to the section "Basic and Translational Cardiovascular Research".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 38668

Special Issue Editors

Dr. Sean M. Wu

E-Mail Website
Guest Editor
Lokey Stem Cell Building, G1120A, Stanford Cardiovascular Institute, 265, Campus Dr, Stanford, CA 94305, USA
Interests: cardiac progenitor cell; cardiac development; transcriptional regulation; Nkx2-5; myocardial regeneration; induced pluripotent stem cell
Special Issues, Collections and Topics in MDPI journals
Dr. Vahid Serpooshan

E-Mail Website
Guest Editor
Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA 30322, USA
Interests: cardiovascular tissue engineering; 3D bioprinting; nano-biomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of JCDD is focused on “Cardiovascular Tissue Engineering”, encompassing the variety of biomaterial, cellular, and hybrid mechanisms of engineering cardiovascular tissue constructs for in vitro disease modeling and drug screening, as well as in vivo regenerative applications. Cardiovascular tissue engineering has emerged and evolved as one of the most promising fields of cardiovascular research, at the intersection of scientific fields in biology, physical and materials sciences, and bioengineering. Functional biomaterial systems are designed and fabricated, using a variety of advanced tissue manufacturing methods to recpaitulate the native cardiac tissue extracellualr matrix. These cardiac biomaterials influence the behavior of cells through a complex array of physiomechanical and biohemical cues. The geometry, dimensions, and chemistry of cardiac scaffolds affect processes such as cell attachment, proliferation, differentiation, and function. As cardiac and vascular cells flourish in artificial bioengineered environments, they may transform into functional tissues with translational values.

In this Special Issue, we aim to capture state-of-the-art research and review articles focusing on advanced cellular and biomaterial-based approaches of cardiovascular tissue engineering. In particular, we seek novel studies on the development of tissue biomanufacturing methods to create cardiovascular tissue mimics, advanced biomaterial systems designed to model cardiac tissues, and stem cell-based approaches. Applications are not limited to, but include, cardiac patch systems for in vivo tissue regeneration and tissue analogues for in vitro disease modeling and/or drug screening

Prof. Dr. Sean M. Wu
Dr. Vahid Serpooshan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Cardiovascular Development and Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cardiac regeneration
  • Cardiac patch devices
  • Cardiovascular disease modeling and drug screening
  • Cardiac tissue bioprinting
  • In vitro cardiac tissue mimics
  • Cardiac cell therapies

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Published Papers (8 papers)

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Research

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15 pages, 2620 KiB  
Article
Designing a 3D Printing Based Auxetic Cardiac Patch with hiPSC-CMs for Heart Repair
by Olga Brazhkina, Jeong Hun Park, Hyun-Ji Park, Sruti Bheri, Joshua T. Maxwell, Scott J. Hollister and Michael E. Davis
J. Cardiovasc. Dev. Dis. 2021, 8(12), 172; https://doi.org/10.3390/jcdd8120172 - 3 Dec 2021
Cited by 6 | Viewed by 4965
Abstract
Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. [...] Read more.
Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson’s ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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12 pages, 2324 KiB  
Article
Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
by Sruti Bheri, Brandon P. Kassouf, Hyun-Ji Park, Jessica R. Hoffman and Michael E. Davis
J. Cardiovasc. Dev. Dis. 2021, 8(11), 135; https://doi.org/10.3390/jcdd8110135 - 22 Oct 2021
Cited by 7 | Viewed by 2793
Abstract
Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within [...] Read more.
Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within a complex membrane and improve cardiac outcomes similar to that of their parent cells. However, miRNA loading efficiency is low, and sEV yield and cargo composition vary with parent cell conditions, minimizing sEV potency. Synthetic mimics allow for cargo-loading control but consist of much simpler membranes, often suffering from high immunogenicity and poor stability. Here, we aim to combine the benefits of sEVs and synthetic mimics to develop sEV-like vesicles (ELVs) with customized cargo loading. We developed a modified thin-film hydration (TFH) mechanism to engineer ELVs from CPC-derived sEVs with pro-angiogenic miR-126 encapsulated. Characterization shows miR-126+ ELVs are similar in size and structure to sEVs. Upon administration to cardiac endothelial cells (CECs), ELV uptake is similar to sEVs too. Further, when functionally validated with a CEC tube formation assay, ELVs significantly improve tube formation parameters compared to sEVs. This study shows TFH-ELVs synthesized from sEVs allow for select miRNA loading and can improve in vitro cardiac outcomes. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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Review

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11 pages, 1538 KiB  
Review
Cardiac Organoids and Gastruloids to Study Physio-Pathological Heart Development
by Marisa E. Jaconi and Michel Puceat
J. Cardiovasc. Dev. Dis. 2021, 8(12), 178; https://doi.org/10.3390/jcdd8120178 - 10 Dec 2021
Cited by 2 | Viewed by 4183
Abstract
Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human [...] Read more.
Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human gastruloids and the cardiac organoids. While the first one mainly recapitulates the gastrulation and is still limited to investigate cardiac development, the second one is becoming more and more helpful to mimic a functional beating heart. The review reports and discusses seminal works in the fields of human gastruloids and cardiac organoids. It further describes technologies which improve the formation of cardiac organoids. Finally, we propose some lines of research towards the building of beating mini-hearts in vitro for more relevant functional studies. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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14 pages, 316 KiB  
Review
Cardiac Tissue Engineering for the Treatment of Myocardial Infarction
by Dongmin Yu, Xiaowei Wang and Lei Ye
J. Cardiovasc. Dev. Dis. 2021, 8(11), 153; https://doi.org/10.3390/jcdd8110153 - 8 Nov 2021
Cited by 7 | Viewed by 3427
Abstract
Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic [...] Read more.
Poor cell engraftment rate is one of the primary factors limiting the effectiveness of cell transfer therapy for cardiac repair. Recent studies have shown that the combination of cell-based therapy and tissue engineering technology can improve stem cell engraftment and promote the therapeutic effects of the treatment for myocardial infarction. This mini-review summarizes the recent progress in cardiac tissue engineering of cardiovascular cells from differentiated human pluripotent stem cells (PSCs), highlights their therapeutic applications for the treatment of myocardial infarction, and discusses the present challenges of cardiac tissue engineering and possible future directions from a clinical perspective. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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32 pages, 1693 KiB  
Review
Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions
by Jee Eun Oh, Cholomi Jung and Young-sup Yoon
J. Cardiovasc. Dev. Dis. 2021, 8(11), 148; https://doi.org/10.3390/jcdd8110148 - 4 Nov 2021
Cited by 12 | Viewed by 4543
Abstract
Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). [...] Read more.
Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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25 pages, 2280 KiB  
Review
Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering
by Astha Khanna, Maedeh Zamani and Ngan F. Huang
J. Cardiovasc. Dev. Dis. 2021, 8(11), 137; https://doi.org/10.3390/jcdd8110137 - 22 Oct 2021
Cited by 34 | Viewed by 8690
Abstract
Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic [...] Read more.
Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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16 pages, 25841 KiB  
Review
Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration
by Angello Huerta Gomez, Sanika Joshi, Yong Yang, Johnathan D. Tune, Ming-Tao Zhao and Huaxiao Yang
J. Cardiovasc. Dev. Dis. 2021, 8(10), 125; https://doi.org/10.3390/jcdd8100125 - 30 Sep 2021
Cited by 8 | Viewed by 3706
Abstract
The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling [...] Read more.
The Notch intercellular signaling pathways play significant roles in cardiovascular development, disease, and regeneration through modulating cardiovascular cell specification, proliferation, differentiation, and morphogenesis. The dysregulation of Notch signaling leads to malfunction and maldevelopment of the cardiovascular system. Currently, most findings on Notch signaling rely on animal models and a few clinical studies, which significantly bottleneck the understanding of Notch signaling-associated human cardiovascular development and disease. Recent advances in the bioengineering systems and human pluripotent stem cell-derived cardiovascular cells pave the way to decipher the role of Notch signaling in cardiovascular-related cells (endothelial cells, cardiomyocytes, smooth muscle cells, fibroblasts, and immune cells), and intercellular crosstalk in the physiological, pathological, and regenerative context of the complex human cardiovascular system. In this review, we first summarize the significant roles of Notch signaling in individual cardiac cell types. We then cover the bioengineering systems of microfluidics, hydrogel, spheroid, and 3D bioprinting, which are currently being used for modeling and studying Notch signaling in the cardiovascular system. At last, we provide insights into ancillary supports of bioengineering systems, varied types of cardiovascular cells, and advanced characterization approaches in further refining Notch signaling in cardiovascular development, disease, and regeneration. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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Other

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13 pages, 5984 KiB  
Brief Report
Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes
by Qianliang Yuan, Renee G. C. Maas, Ellen C. J. Brouwer, Jiayi Pei, Christian Snijders Blok, Marko A. Popovic, Nanne J. Paauw, Niels Bovenschen, Jesper Hjortnaes, Magdalena Harakalova, Pieter A. Doevendans, Joost P. G. Sluijter, Jolanda van der Velden and Jan W. Buikema
J. Cardiovasc. Dev. Dis. 2022, 9(2), 43; https://doi.org/10.3390/jcdd9020043 - 27 Jan 2022
Cited by 4 | Viewed by 4902
Abstract
Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during [...] Read more.
Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mitosis resulting in cellular or nuclear division in a source of proliferating human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed that both mono- and binuclear hiPSC-CMs give rise to mononuclear daughter cells or binuclear progeny. Within this source of highly proliferative hiPSC-CMs, treated with the CHIR99021 small molecule, we found that Wnt and Hippo signaling was more present when compared to metabolic matured non-proliferative hiPSC-CMs and adult human heart tissue. Furthermore, we found that CHIR99021 increased the efficiency of non-viral vector incorporation in high-proliferative hiPSC-CMs, in which fluorescent transgene expression became present after the chromosomal segregation (M phase). This study provides a tool for gene manipulation studies in hiPSC-CMs and engineered cardiac tissue. Moreover, our data illustrate that there is a complex biology behind the cellular and nuclear division of mono- and binuclear CMs, with a shared-phenomenon of sarcomere disassembly during mitosis. Full article
(This article belongs to the Special Issue Cardiovascular Tissue Engineering)
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