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Bioengineering
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Advances in Cardiovascular Tissue-Engineering
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Advances in Cardiovascular 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 May 2024) | Viewed by 19556

Special Issue Editors

Dr. Rouven Berndt

E-Mail Website
Guest Editor
Clinic of Cardiovascular Surgery, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
Interests: bioengineering of cardiovascular implants and therapeutics; ATMPs; cell and gene therapy; angiogenesis; ischemic and reperfusion injury; translational cardiovascular medicine
Dr. Chung-Hao Lee

E-Mail Website
Guest Editor
Department of Bioengineering, University of California, Riverside, CA 92521, USA
Interests: cardiovascular heart valve biomechanics; multi-scale modeling; biomaterials design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The regenerative ability of the human body is limited, and the number of tissue and organ donations has been declining for years, while the morbidity and mortality rates of cardiovascular disease have been increasing. Cardiovascular tissue engineering theoretically offers the possibility of treating a wide range of structural diseases of the heart and vascular system. However, to date, cardiovascular tissue engineering is not yet ready for routine clinical use. However, the rapid development of various techniques in basic research, engineering, and translational medicine have raised the legitimate hope of improving the future therapy of cardiovascular diseases.

In addition to holistic organ transplantation, many approaches focus on the stepwise regeneration or bioartificial replacement of partial cardiovascular structures, e.g., heart valves, cardiac patches, bioartificial vessels, or stem cell transplantation in areas of myocardial infarction.

In addition to the technical challenges of biological manufacturing, the current focus is also on the risks of these future therapies; tumorigenicity, graft rejection, immunogenicity, and cell migration are major problems of tissue engineering that have not yet been fully solved.

Therefore, this Special Issue of Bioengineering on the Advances in Cardiovascular Tissue Engineering focuses on the interdisciplinary research in and development of cardiovascular science and engineering by bringing together cutting-edge contributions from worldwide experts on translational medicine, engineering, cell and gene therapy, bioprinting, bioreactor design, bioprocess development, and the manufacturing of stem-cell-based therapies.

Dr. Rouven Berndt
Dr. Chung-Hao Lee
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
  • bioengineering
  • tissue-engineering
  • ATMPs
  • cell and gene therapy
  • peripheral arterial disease
  • stem cells
  • heart valve, myocardial infarction
  • bioartificial organs
  • 3D-bioprinting
  • bioreactor
  • regenerative medicine
  • translational medicine

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Published Papers (6 papers)

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Research

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17 pages, 15365 KiB  
Article
Intramyocardial Injection of Hypoxia-Conditioned Extracellular Vesicles Modulates Response to Oxidative Stress in the Chronically Ischemic Myocardium
by Dwight D. Harris, Sharif A. Sabe, Mark Broadwin, Cynthia Xu, Christopher Stone, Meghamsh Kanuparthy, Akshay Malhotra, M. Ruhul Abid and Frank W. Sellke
Bioengineering 2024, 11(2), 125; https://doi.org/10.3390/bioengineering11020125 - 28 Jan 2024
Cited by 2 | Viewed by 1548
Abstract
Introduction: Patients with advanced coronary artery disease (CAD) who are not eligible for stenting or surgical bypass procedures have limited treatment options. Extracellular vesicles (EVs) have emerged as a potential therapeutic target for the treatment of advanced CAD. These EVs can be conditioned [...] Read more.
Introduction: Patients with advanced coronary artery disease (CAD) who are not eligible for stenting or surgical bypass procedures have limited treatment options. Extracellular vesicles (EVs) have emerged as a potential therapeutic target for the treatment of advanced CAD. These EVs can be conditioned to modify their contents. In our previous research, we demonstrated increased perfusion, decreased inflammation, and reduced apoptosis with intramyocardial injection of hypoxia-conditioned EVs (HEVs). The goal of this study is to further understand the function of HEVs by examining their impact on oxidative stress using our clinically relevant and extensively validated swine model of chronic myocardial ischemia. Methods: Fourteen Yorkshire swine underwent a left thoracotomy for the placement of an ameroid constrictor on the left circumflex coronary artery to model chronic myocardial ischemia. After two weeks of recovery, the swine underwent a redo thoracotomy with injection of either HEVs (n = 7) or a saline control (CON, n = 7) into the ischemic myocardium. Five weeks after injection, the swine were subjected to terminal harvest. Protein expression was measured using immunoblotting. OxyBlot analysis and 3-nitrotyrosine staining were used to quantify total oxidative stress. Results: There was a significant increase in myocardial expression of the antioxidants SOD 2, GPX-1, HSF-1, UCP-2, catalase, and HO-1 (all p ≤ 0.05) in the HEV group when compared to control animals. The HEVs also exhibited a significant increase in pro-oxidant NADPH oxidase (NOX) 1, NOX 3, p47phox, and p67phox (all p ≤ 0.05). However, no change was observed in the expression of NFkB, KEAP 1, and PRDX1 (all p > 0.05) between the HEV and CON groups. There were no significant differences in total oxidative stress as determined by OxyBlot and 3-nitrotyrosine staining (p = 0.64, p = 0.32) between the groups. Conclusions: Administration of HEVs in ischemic myocardium induces a significant increase in pro- and antioxidant proteins without a net change in total oxidative stress. These findings suggest that HEV-induced changes in redox signaling pathways may play a role in increased perfusion, decreased inflammation, and reduced apoptosis in ischemic myocardium. Further studies are required to determine if HEVs alter the net oxidative stress in ischemic myocardium at an earlier time point of HEV administration. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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17 pages, 6834 KiB  
Article
Characterization of a Decellularized Sheep Pulmonary Heart Valves and Analysis of Their Capability as a Xenograft Initial Matrix Material in Heart Valve Tissue Engineering
by Müslüm Süleyman İnal, Cihan Darcan and Ali Akpek
Bioengineering 2023, 10(8), 949; https://doi.org/10.3390/bioengineering10080949 - 9 Aug 2023
Cited by 2 | Viewed by 2037
Abstract
In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving [...] Read more.
In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving the natural tissue architecture. SD and SDS are detergent derivatives frequently used in decellularization studies. The aim of our study is to decellularize the pulmonary heart valves of young Merino sheep by using low-density SDS and SD detergents together, and then to perform their detailed characterization to determine whether they are suitable for clinical studies. Pulmonary heart valves of 4–6-month-old sheep were decellularized in detergent solution for 24 h. The amount of residual DNA was measured to determine the efficiency of decellularization. Then, the effect of decellularization on the ECM by histological staining was examined. In addition, the samples were visualized by SEM to determine the surface morphologies of the scaffolds. A uniaxial tensile test was performed to examine the effect of decellularization on biomechanical properties. In vitro stability of scaffolds decellularized by collagenase treatment was determined. In addition, the cytotoxic effect of scaffolds on 3T3 cells was examined by MTT assay. The results showed DNA removal of 94% and 98% from the decellularized leaflet and pulmonary wall portions after decellularization relative to the control group. No cell nuclei were found in histological staining and it was observed that the three-layer leaflet structure was preserved. As a result of the tensile test, it was determined that there was no statistically significant difference between the control and decellularized groups in the UTS and elasticity modulus, and the biomechanical properties did not change. It was also observed that decellularized sheep pulmonary heart valves had no cytotoxic effect. In conclusion, we suggest that the pulmonary valves of decellularized young Merino sheep can be used as an initial matrix in heart valve tissue engineering studies. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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19 pages, 21111 KiB  
Article
Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
by Fatemeh Navaee, Philippe Renaud, Niccolò Piacentini, Mathilde Durand, Dara Zaman Bayat, Diane Ledroit, Sarah Heub, Stephanie Boder-Pasche, Alexander Kleger, Thomas Braschler and Gilles Weder
Bioengineering 2023, 10(2), 266; https://doi.org/10.3390/bioengineering10020266 - 17 Feb 2023
Cited by 1 | Viewed by 2924
Abstract
Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, creating a dominant orientation. Additionally, local [...] Read more.
Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, creating a dominant orientation. Additionally, local alignments of fibers, along with a helical organization, become evident at the macroscopic level. For the successful development of a reliable in vitro cardiac model, evaluation of cardiac cells’ behavior in a dynamic microenvironment, as well as their spatial architecture, is mandatory. In this study, we hypothesize that complex interactions between long-term contraction boundary conditions and cyclic mechanical stimulation may provide a physiological mechanism to generate off-axis alignments in the preferred mechanical stretch direction. This off-axis alignment can be engineered in vitro and, most importantly, mirrors the helical arrangements observed in vivo. For this purpose, uniaxial mechanical stretching of dECM-fibrin hydrogels was performed on pre-aligned 3D cultures of cardiac cells. In view of the potential development of helical structures similar to those in native hearts, the possibility of generating oblique alignments ranging between 0° and 90° was explored. Indeed, our investigations of cell alignment in 3D, employing both mechanical stimulation and groove constraint, provide a reliable mechanism for the generation of helicoidal structures in the myocardium. By combining cyclic stretch and geometric alignment in grooves, an intermediate angle toward favored direction can be achieved experimentally: while cyclic stretch produces a perpendicular orientation, geometric alignment is associated with a parallel one. In our 2D and 3D culture conditions, nonlinear cellular addition of the strains and strain avoidance concept reliably predicted the preferred cellular alignment. The 3D dECM-fibrin model system in this study shows that cyclical stretching supports cell survival and development. Using mechanical stimulation of pre-aligned heart cells, maturation markers are augmented in neonatal cardiomyocytes, while the beating culture period is prolonged, indicating an improved model function. We propose a simplified theoretical model based on numerical simulation and nonlinear strain avoidance by cells to explain oblique alignment angles. Thus, this work lays a possible rational basis for understanding and engineering oblique cellular alignments, such as the helicoidal layout of the heart, using approaches that simultaneously enhance maturation and function. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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Review

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21 pages, 1676 KiB  
Review
The Application of Porous Scaffolds for Cardiovascular Tissues
by Tatsuya Watanabe, Salha Sassi, Anudari Ulziibayar, Rikako Hama, Takahiro Kitsuka and Toshiharu Shinoka
Bioengineering 2023, 10(2), 236; https://doi.org/10.3390/bioengineering10020236 - 10 Feb 2023
Cited by 3 | Viewed by 2728
Abstract
As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability [...] Read more.
As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability of the artificial organs. Therefore, tissue engineering has attracted significant attention as a tissue regeneration therapy in this area. Porous scaffolds are one of the effective methods for tissue engineering. However, it could be better, and its effectiveness varies depending on the tissue application. This paper will address the challenges presented by various materials and their combinations. We will also describe some of the latest methods for tissue engineering. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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37 pages, 1101 KiB  
Review
Whole-Heart Tissue Engineering and Cardiac Patches: Challenges and Promises
by Aram Akbarzadeh, Soheila Sobhani, Alireza Soltani Khaboushan and Abdol-Mohammad Kajbafzadeh
Bioengineering 2023, 10(1), 106; https://doi.org/10.3390/bioengineering10010106 - 12 Jan 2023
Cited by 12 | Viewed by 6316
Abstract
Despite all the advances in preventing, diagnosing, and treating cardiovascular disorders, they still account for a significant part of mortality and morbidity worldwide. The advent of tissue engineering and regenerative medicine has provided novel therapeutic approaches for the treatment of various diseases. Tissue [...] Read more.
Despite all the advances in preventing, diagnosing, and treating cardiovascular disorders, they still account for a significant part of mortality and morbidity worldwide. The advent of tissue engineering and regenerative medicine has provided novel therapeutic approaches for the treatment of various diseases. Tissue engineering relies on three pillars: scaffolds, stem cells, and growth factors. Gene and cell therapy methods have been introduced as primary approaches to cardiac tissue engineering. Although the application of gene and cell therapy has resulted in improved regeneration of damaged cardiac tissue, further studies are needed to resolve their limitations, enhance their effectiveness, and translate them into the clinical setting. Scaffolds from synthetic, natural, or decellularized sources have provided desirable characteristics for the repair of cardiac tissue. Decellularized scaffolds are widely studied in heart regeneration, either as cell-free constructs or cell-seeded platforms. The application of human- or animal-derived decellularized heart patches has promoted the regeneration of heart tissue through in vivo and in vitro studies. Due to the complexity of cardiac tissue engineering, there is still a long way to go before cardiac patches or decellularized whole-heart scaffolds can be routinely used in clinical practice. This paper aims to review the decellularized whole-heart scaffolds and cardiac patches utilized in the regeneration of damaged cardiac tissue. Moreover, various decellularization methods related to these scaffolds will be discussed. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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21 pages, 1079 KiB  
Review
Epigenetics and Gut Microbiota Crosstalk: A potential Factor in Pathogenesis of Cardiovascular Disorders
by Vineet Mehta, Priyanka Nagu, Baskaran Stephen Inbaraj, Minaxi Sharma, Arun Parashar and Kandi Sridhar
Bioengineering 2022, 9(12), 798; https://doi.org/10.3390/bioengineering9120798 - 13 Dec 2022
Cited by 5 | Viewed by 3091
Abstract
Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and “sudden death” globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more [...] Read more.
Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and “sudden death” globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more evident as its direct involvement has been reported. The discovery of epigenetic mechanisms, such as DNA methylation and histone modification, suggested that external factors could alter gene expression to modulate human health. These external factors also influence our gut microbiota (GM), which participates in multiple metabolic processes in our body. Evidence suggests a high association of GM with CVDs. Although the exact mechanism remains unclear, the influence of GM over the epigenetic mechanisms could be one potential pathway in CVD etiology. Both epigenetics and GM are dynamic processes and vary with age and environment. Changes in the composition of GM have been found to underlie the pathogenesis of metabolic diseases via modulating epigenetic changes in the form of DNA methylation, histone modifications, and regulation of non-coding RNAs. Several metabolites produced by the GM, including short-chain fatty acids, folates, biotin, and trimethylamine-N-oxide, have the potential to regulate epigenetics, apart from playing a vital role in normal physiological processes. The role of GM and epigenetics in CVDs are promising areas of research, and important insights in the field of early diagnosis and therapeutic approaches might appear soon. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Tissue-Engineering)
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