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Bioengineering
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Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to...
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Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 38208

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Panagiotis Mallis

E-Mail Website
Guest Editor
Department of Tissue Engineering and Regenerative Medicine of Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens (BRFAA), 11527 Athina, Greece
Interests: immunobiology of stem cells; molecular genetics of HLA; tissue-engineered small-diameter vascular grafts; immunobiology of biological scaffolds; mesenchymal stromal cells; hematopoietic stem cells biology
Special Issues, Collections and Topics in MDPI journals
Dr. Efstathios Michalopoulos

E-Mail Website
Guest Editor
Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens (BRFAA), Athens, Greece
Interests: tissue engineering; regenerative medicine; mesenchymal stromal cells; hematopoietic stem cells; vascular grafts; immunobiology; platelet gel
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular disease (CAD) is the leading cause of death, globally, of all the non-communicable diseases. CAD is a group of complex disorders which includes peripheral arterial disease, coronary heart disease, cerebrovascular disease, and rheumatic heart disease. Each year, more than 800,000 bypass surgeries are performed. Additionally, it is speculated that more than 17 million of people have died due to CAD, representing approximately 31% of all deaths worldwide.

 It has been speculated that CAD costs the European Union (EU) more than 210 billion euros, and more than 300 billion dollars in the case of the United States of America (USA). The primary cause for the development of CAD is atherogenesis and developed atherosclerosis, which induces functional alterations to the vessels of the circulatory system. In this process, an individual’s genetic background may influence the progression of this disease. Indeed, among other factors, genetic alterations regarding the function of immune cells and the human leukocyte antigen (HLA) system play a crucial role in the pathogenesis of CAD. In better understanding better an individual’s genetic alterations, which are specific for the initiation and progression of CAD, novel targets for advanced therapeutics may be revealed.

Advanced approaches for CAD prevention also involve the use of suitable tissue-engineered vascular grafts (TEVG) for bypass surgeries. The gold standard conduits for this purpose are the Dacron- or ePTFE-derived vascular grafts. In addition, autologous grafts, such as saphenous vein, have also been applied in the past. Unfortunately, less than 40% of patients have autologous vessels suitable for this purpose. Additionally, animal-derived vessels have been tested for their suitability as conduits. Recently, the production of TEVG using decellularization methods has gained significant attention from the scientific society. In the aforementioned approaches, the mechanical properties of the produced grafts are at the center of the attention, and their study may reveal valuable information regarding their structure–function properties.

Modern approaches for CAD will take into account individual’s own characteristics, promoting, in this way, advanced personalized therapeutic strategies in accordance with the conditions of good manufacturing practices (GMP).

We are delighted to present the current Special Issue entitled “Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering”. This collection of articles will involve the most relevant and state-of-the-art research related to the topic of the Special Issue, including:

  • Molecular analysis of cardiovascular disease
  • Novel biomarkers of cardiovascular disease
  • Population genetics and association with cardiovascular disease
  • Novel approaches for cardiovascular disease administration
  • Vascular grafts and their application in cardiovascular disease
  • Biomechanical properties of TEVG

We invite researchers to submit original research articles, short communications, reviews, and opinion articles that meet the aim of the current Special Issue. We look forward to receiving your valuable contributions.

Dr. Panagiotis Mallis
Dr. Efstathios Michalopoulos
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. Bioengineering 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

  • cardiovascular disease
  • biomarkers
  • genetic alterations
  • HLA
  • TEVG
  • biomechanics
  • GMPs

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Published Papers (5 papers)

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Editorial

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4 pages, 198 KiB  
Editorial
Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering
by Panagiotis Mallis, Efstathios Michalopoulos and Catherine Stavropoulos-Giokas
Bioengineering 2021, 8(11), 174; https://doi.org/10.3390/bioengineering8110174 - 4 Nov 2021
Cited by 4 | Viewed by 2354
Abstract
Cardiovascular disease (CVD) currently represents one of the leading causes of death worldwide. It is estimated that more than 17.9 million people die each year due to CVD manifestations. Often, occlusion or stenosis of the vascular network occurs, either in large- or small-diameter [...] Read more.
Cardiovascular disease (CVD) currently represents one of the leading causes of death worldwide. It is estimated that more than 17.9 million people die each year due to CVD manifestations. Often, occlusion or stenosis of the vascular network occurs, either in large- or small-diameter blood vessels. Moreover, the obstruction of small vessels such as the coronary arteries may be related to more pronounced events, which can be life-threatening. The gold standard procedure utilizes the transplantation of secondary vessels or the use of synthetic vascular grafts. However, significant adverse reactions have accompanied the use of the above grafts. Therefore, modern therapeutic strategies must be evaluated for better disease administration. In the context of alternative therapies, advanced tissue-engineering approaches including the decellularization procedure and the 3D additive bioprinting methods, have been proposed. In this way the availability of bioengineered vascular grafts will be increased, covering the great demand that exists globally. In this Special Issue of Bioengineering, we tried to highlight the modern approaches which are focused on CVD therapeutics. This issue includes articles related to the efficient development of vascular grafts, 3D printing approaches and suitable atherosclerosis models. Full article
(This article belongs to the Special Issue Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering)

Research

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22 pages, 107896 KiB  
Article
Improved Repopulation Efficacy of Decellularized Small Diameter Vascular Grafts Utilizing the Cord Blood Platelet Lysate
by Panagiotis Mallis, Dimitrios P. Sokolis, Michalis Katsimpoulas, Alkiviadis Kostakis, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos
Bioengineering 2021, 8(9), 118; https://doi.org/10.3390/bioengineering8090118 - 27 Aug 2021
Cited by 2 | Viewed by 4184
Abstract
Background: The development of functional bioengineered small-diameter vascular grafts (SDVGs), represents a major challenge of tissue engineering. This study aimed to evaluate the repopulation efficacy of biological vessels, utilizing the cord blood platelet lysate (CBPL). Methods: Human umbilical arteries (hUAs, n = 10) [...] Read more.
Background: The development of functional bioengineered small-diameter vascular grafts (SDVGs), represents a major challenge of tissue engineering. This study aimed to evaluate the repopulation efficacy of biological vessels, utilizing the cord blood platelet lysate (CBPL). Methods: Human umbilical arteries (hUAs, n = 10) were submitted to decellularization. Then, an evaluation of decellularized hUAs, involving histological, biochemical and biomechanical analysis, was performed. Wharton’s Jelly (WJ) Mesenchymal Stromal Cells (MSCs) were isolated and characterized for their properties. Then, WJ-MSCs (1.5 × 106 cells) were seeded on decellularized hUAs (n = 5) and cultivated with (Group A) or without the presence of the CBPL, (Group B) for 30 days. Histological analysis involving immunohistochemistry (against Ki67, for determination of cell proliferation) and indirect immunofluorescence (against activated MAP kinase, additional marker for cell growth and proliferation) was performed. Results: The decellularized hUAs retained their initial vessel’s properties, in terms of key-specific proteins, the biochemical and biomechanical characteristics were preserved. The evaluation of the repopulation process indicated a more uniform distribution of WJ-MSCs in group A compared to group B. The repopulated vascular grafts of group B were characterized by greater Ki67 and MAP kinase expression compared to group A. Conclusion: The results of this study indicated that the CBPL may improve the repopulation efficacy, thus bringing the biological SDVGs one step closer to clinical application. Full article
(This article belongs to the Special Issue Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering)
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20 pages, 2746 KiB  
Article
Biomimetic 3D Models for Investigating the Role of Monocytes and Macrophages in Atherosclerosis
by Anna Garcia-Sabaté, Walaa Kamal E. Mohamed, Jiranuwat Sapudom, Aseel Alatoom, Layla Al Safadi and Jeremy C. M. Teo
Bioengineering 2020, 7(3), 113; https://doi.org/10.3390/bioengineering7030113 - 16 Sep 2020
Cited by 30 | Viewed by 15034
Abstract
Atherosclerosis, the inflammation of artery walls due to the accumulation of lipids, is the most common underlying cause for cardiovascular diseases. Monocytes and macrophages are major cells that contribute to the initiation and progression of atherosclerotic plaques. During this process, an accumulation of [...] Read more.
Atherosclerosis, the inflammation of artery walls due to the accumulation of lipids, is the most common underlying cause for cardiovascular diseases. Monocytes and macrophages are major cells that contribute to the initiation and progression of atherosclerotic plaques. During this process, an accumulation of LDL-laden macrophages (foam cells) and an alteration in the extracellular matrix (ECM) organization leads to a local vessel stiffening. Current in vitro models are carried out onto two-dimensional tissue culture plastic and cannot replicate the relevant microenvironments. To bridge the gap between in vitro and in vivo conditions, we utilized three-dimensional (3D) collagen matrices that allowed us to mimic the ECM stiffening during atherosclerosis by increasing collagen density. First, human monocytic THP-1 cells were embedded into 3D collagen matrices reconstituted at low and high density. Cells were subsequently differentiated into uncommitted macrophages (M0) and further activated into pro- (M1) and anti-inflammatory (M2) phenotypes. In order to mimic atherosclerotic conditions, cells were cultured in the presence of oxidized LDL (oxLDL) and analyzed in terms of oxLDL uptake capability and relevant receptors along with their cytokine secretomes. Although oxLDL uptake and larger lipid size could be observed in macrophages in a matrix dependent manner, monocytes showed higher numbers of oxLDL uptake cells. By analyzing major oxLDL uptake receptors, both monocytes and macrophages expressed lectin-like oxidized low-density lipoprotein receptor-1 (LOX1), while enhanced expression of scavenger receptor CD36 could be observed only in M2. Notably, by analyzing the secretome of macrophages exposed to oxLDL, we demonstrated that the cells could, in fact, secrete adipokines and growth factors in distinct patterns. Besides, oxLDL appeared to up-regulate MHCII expression in all cells, while an up-regulation of CD68, a pan-macrophage marker, was found only in monocytes, suggesting a possible differentiation of monocytes into a pro-inflammatory macrophage. Overall, our work demonstrated that collagen density in the plaque could be one of the major factors driving atherosclerotic progression via modulation of monocyte and macrophages behaviors. Full article
(This article belongs to the Special Issue Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering)
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Review

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13 pages, 474 KiB  
Review
Recent Advancements in 3D Printing and Bioprinting Methods for Cardiovascular Tissue Engineering
by Foteini K. Kozaniti, Despoina Nektaria Metsiou, Aikaterini E. Manara, George Athanassiou and Despina D. Deligianni
Bioengineering 2021, 8(10), 133; https://doi.org/10.3390/bioengineering8100133 - 27 Sep 2021
Cited by 17 | Viewed by 6677
Abstract
Recent decades have seen a plethora of regenerating new tissues in order to treat a multitude of cardiovascular diseases. Autografts, xenografts and bioengineered extracellular matrices have been employed in this endeavor. However, current limitations of xenografts and exogenous scaffolds to acquire sustainable cell [...] Read more.
Recent decades have seen a plethora of regenerating new tissues in order to treat a multitude of cardiovascular diseases. Autografts, xenografts and bioengineered extracellular matrices have been employed in this endeavor. However, current limitations of xenografts and exogenous scaffolds to acquire sustainable cell viability, anti-inflammatory and non-cytotoxic effects with anti-thrombogenic properties underline the requirement for alternative bioengineered scaffolds. Herein, we sought to encompass the methods of biofabricated scaffolds via 3D printing and bioprinting, the biomaterials and bioinks recruited to create biomimicked tissues of cardiac valves and vascular networks. Experimental and computational designing approaches have also been included. Moreover, the in vivo applications of the latest studies on the treatment of cardiovascular diseases have been compiled and rigorously discussed. Full article
(This article belongs to the Special Issue Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering)
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40 pages, 1631 KiB  
Review
Future Perspectives in Small-Diameter Vascular Graft Engineering
by Panagiotis Mallis, Alkiviadis Kostakis, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos
Bioengineering 2020, 7(4), 160; https://doi.org/10.3390/bioengineering7040160 - 10 Dec 2020
Cited by 76 | Viewed by 8692
Abstract
The increased demands of small-diameter vascular grafts (SDVGs) globally has forced the scientific society to explore alternative strategies utilizing the tissue engineering approaches. Cardiovascular disease (CVD) comprises one of the most lethal groups of non-communicable disorders worldwide. It has been estimated that in [...] Read more.
The increased demands of small-diameter vascular grafts (SDVGs) globally has forced the scientific society to explore alternative strategies utilizing the tissue engineering approaches. Cardiovascular disease (CVD) comprises one of the most lethal groups of non-communicable disorders worldwide. It has been estimated that in Europe, the healthcare cost for the administration of CVD is more than 169 billion €. Common manifestations involve the narrowing or occlusion of blood vessels. The replacement of damaged vessels with autologous grafts represents one of the applied therapeutic approaches in CVD. However, significant drawbacks are accompanying the above procedure; therefore, the exploration of alternative vessel sources must be performed. Engineered SDVGs can be produced through the utilization of non-degradable/degradable and naturally derived materials. Decellularized vessels represent also an alternative valuable source for the development of SDVGs. In this review, a great number of SDVG engineering approaches will be highlighted. Importantly, the state-of-the-art methodologies, which are currently employed, will be comprehensively presented. A discussion summarizing the key marks and the future perspectives of SDVG engineering will be included in this review. Taking into consideration the increased number of patients with CVD, SDVG engineering may assist significantly in cardiovascular reconstructive surgery and, therefore, the overall improvement of patients’ life. Full article
(This article belongs to the Special Issue Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering)
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