scholarly journals Engineering Human Cardiac Muscle Patch Constructs for Prevention of Post-infarction LV Remodeling

2021 ◽  
Vol 8 ◽  
Author(s):  
Lu Wang ◽  
Vahid Serpooshan ◽  
Jianyi Zhang
Keyword(s):  
Tissue Engineering ◽  
Cardiac Muscle ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
Disease Modeling ◽  
Cell Types ◽  
Cardiac Cells ◽  
Spatiotemporal Resolution ◽  
Lv Remodeling

Tissue engineering combines principles of engineering and biology to generate living tissue equivalents for drug testing, disease modeling, and regenerative medicine. As techniques for reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) and subsequently differentiating them into cardiomyocytes and other cardiac cells have become increasingly efficient, progress toward the development of engineered human cardiac muscle patch (hCMP) and heart tissue analogs has accelerated. A few pilot clinical studies in patients with post-infarction LV remodeling have been already approved. Conventional methods for hCMP fabrication include suspending cells within scaffolds, consisting of biocompatible materials, or growing two-dimensional sheets that can be stacked to form multilayered constructs. More recently, advanced technologies, such as micropatterning and three-dimensional bioprinting, have enabled fabrication of hCMP architectures at unprecedented spatiotemporal resolution. However, the studies working on various hCMP-based strategies for in vivo tissue repair face several major obstacles, including the inadequate scalability for clinical applications, poor integration and engraftment rate, and the lack of functional vasculature. Here, we review many of the recent advancements and key concerns in cardiac tissue engineering, focusing primarily on the production of hCMPs at clinical/industrial scales that are suitable for administration to patients with myocardial disease. The wide variety of cardiac cell types and sources that are applicable to hCMP biomanufacturing are elaborated. Finally, some of the key challenges remaining in the field and potential future directions to address these obstacles are discussed.

scholarly journals Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 563
Author(s):  
Magali Seguret ◽  
Eva Vermersch ◽  
Charlène Jouve ◽  
Jean-Sébastien Hulot
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells ◽  
Cardiac Functions ◽  
Different Types ◽  
Recent Developments ◽  
Human Cardiac Tissue ◽  
Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

scholarly journals Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

Micromachines ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 386
Author(s):  
Ana Santos ◽  
Yongjun Jang ◽  
Inwoo Son ◽  
Jongseong Kim ◽  
Yongdoo Park
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Computational Modeling ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Heart Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

scholarly journals Intrinsically Conductive Polymers for Striated Cardiac Muscle Repair

2021 ◽  
Vol 22 (16) ◽  
pp. 8550
Author(s):  
Arsalan Ul Haq ◽  
Felicia Carotenuto ◽  
Fabio De Matteis ◽  
Paolo Prosposito ◽  
Roberto Francini ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cardiac Muscle ◽  
Cardiac Tissue ◽  
Cultured Cells ◽  
Conductive Polymers ◽  
Signal Propagation ◽  
Scar Tissue ◽  
Cardiac Tissue Engineering ◽  
Conductive Component

One of the most important features of striated cardiac muscle is the excitability that turns on the excitation-contraction coupling cycle, resulting in the heart blood pumping function. The function of the heart pump may be impaired by events such as myocardial infarction, the consequence of coronary artery thrombosis due to blood clots or plaques. This results in the death of billions of cardiomyocytes, the formation of scar tissue, and consequently impaired contractility. A whole heart transplant remains the gold standard so far and the current pharmacological approaches tend to stop further myocardium deterioration, but this is not a long-term solution. Electrically conductive, scaffold-based cardiac tissue engineering provides a promising solution to repair the injured myocardium. The non-conductive component of the scaffold provides a biocompatible microenvironment to the cultured cells while the conductive component improves intercellular coupling as well as electrical signal propagation through the scar tissue when implanted at the infarcted site. The in vivo electrical coupling of the cells leads to a better regeneration of the infarcted myocardium, reducing arrhythmias, QRS/QT intervals, and scar size and promoting cardiac cell maturation. This review presents the emerging applications of intrinsically conductive polymers in cardiac tissue engineering to repair post-ischemic myocardial insult.

scholarly journals Dual-matrix 3D culture system as a biomimetic model of epithelial tissues

2019 ◽  
Author(s):  
Diana Bogorodskaya ◽  
Joshua S. McLane ◽  
Lee A. Ligon
Keyword(s):  
Cell Biology ◽  
Culture System ◽  
Drug Testing ◽  
Disease Modeling ◽  
Wide Spectrum ◽  
3D Culture ◽  
Cell Types ◽  
3D Cultures ◽  
3D Culture System

ABSTRACTRecent years have seen an unprecedented rise in the use of 3D culture systems, both in fundamental research and in more translational settings such as drug testing and disease modeling. However, 3D cultures often remain underused by cell biology labs, both due to technical difficulties in system setup and inherent drawbacks of many of the common systems. Here we describe an easy to use, inexpensive and rapidly assembled 3D culture system, suitable for generation of both normal polarized epithelial cysts and in-situ tumor spheroids. This system allows for exploration of many questions of normal and cancer cell biology, including morphogenesis, epithelial polarization, cell motility, intra- and intercellular communication, invasion, metastasis, and tumor-stoma interaction. The 3D cultures are made up of a stiffness tunable, dual-matrix model that can incorporate co-culture of multiple cell types. The model allows for increased physiological relevance by mimicking the organization, ligand composition and stiffness presentin-vivo. The setup allows for a wide spectrum of manipulation, including removing cells from the system for DNA/protein expression, transfection and high-resolution imaging of live or fixed cells.

scholarly journals Graphene-Based Scaffolds: Fundamentals and Applications for Cardiovascular Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Alex Savchenko ◽  
Rose T. Yin ◽  
Dmitry Kireev ◽  
Igor R. Efimov ◽  
Elena Molokanova
Keyword(s):  
Mechanical Properties ◽  
Electrical Conductivity ◽  
Tissue Engineering ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells ◽  
Great Promise ◽  
Cardiovascular Tissue ◽  
Cell Scaffolds

Cardiac tissue engineering requires materials that can faithfully recapitulate and support the native in vivo microenvironment while providing a seamless bioelectronic interface. Current limitations of cell scaffolds include the lack of electrical conductivity and suboptimal mechanical properties. Here we discuss how the incorporation of graphene into cellular scaffolds, either alone or in combination with other materials, can affect morphology, function, and maturation of cardiac cells. We conclude that graphene-based scaffolds hold great promise for cardiac tissue engineering.

scholarly journals Extrinsically Conductive Nanomaterials for Cardiac Tissue Engineering Applications

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 914
Author(s):  
Arsalan Ul Haq ◽  
Felicia Carotenuto ◽  
Paolo Di Nardo ◽  
Roberto Francini ◽  
Paolo Prosposito ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cardiac Tissue ◽  
Scar Tissue ◽  
Cardiac Tissue Engineering ◽  
Assistive Device ◽  
Long Run ◽  
Fibrotic Scar ◽  
Regeneration Capability ◽  
Conductive Nanomaterials

Myocardial infarction (MI) is the consequence of coronary artery thrombosis resulting in ischemia and necrosis of the myocardium. As a result, billions of contractile cardiomyocytes are lost with poor innate regeneration capability. This degenerated tissue is replaced by collagen-rich fibrotic scar tissue as the usual body response to quickly repair the injury. The non-conductive nature of this tissue results in arrhythmias and asynchronous beating leading to total heart failure in the long run due to ventricular remodelling. Traditional pharmacological and assistive device approaches have failed to meet the utmost need for tissue regeneration to repair MI injuries. Engineered heart tissues (EHTs) seem promising alternatives, but their non-conductive nature could not resolve problems such as arrhythmias and asynchronous beating for long term in-vivo applications. The ability of nanotechnology to mimic the nano-bioarchitecture of the extracellular matrix and the potential of cardiac tissue engineering to engineer heart-like tissues makes it a unique combination to develop conductive constructs. Biomaterials blended with conductive nanomaterials could yield conductive constructs (referred to as extrinsically conductive). These cell-laden conductive constructs can alleviate cardiac functions when implanted in-vivo. A succinct review of the most promising applications of nanomaterials in cardiac tissue engineering to repair MI injuries is presented with a focus on extrinsically conductive nanomaterials.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Bioengineered Cardiac Grafts

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Jonathan Leor ◽  
Sharon Aboulafia-Etzion ◽  
Ayelet Dar ◽  
Lilia Shapiro ◽  
Israel M. Barbash ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Sham Operation ◽  
Complete Disappearance ◽  
3 Dimensional ◽  
Infarcted Myocardium ◽  
Lv Remodeling ◽  
And Function ◽  
Conducive Environment

Background —The myocardium is unable to regenerate because cardiomyocytes cannot replicate after injury. The heart is therefore an attractive target for tissue engineering to replace infarcted myocardium and enhance cardiac function. We tested the feasibility of bioengineering cardiac tissue within novel 3-dimensional (3D) scaffolds. Methods and Results —We isolated and grew fetal cardiac cells within 3D porous alginate scaffolds. The cell constructs were cultured for 4 days to evaluate viability and morphology before implantation. Light microscopy revealed that within 2 to 3 days in culture, the dissociated cardiac cells form distinctive, multicellular contracting aggregates within the scaffold pores. Seven days after myocardial infarction, rats were randomized to biograft implantation (n=6) or sham-operation (n=6) into the myocardial scar. Echocardiography study was performed before and 65±5 days after implantation to assess left ventricular (LV) remodeling and function. Hearts were harvested 9 weeks after implantation. Visual examination of the biograft revealed intensive neovascularization from the neighboring coronary network. Histological examination revealed the presence of myofibers embedded in collagen fibers and a large number of blood vessels. The specimens showed almost complete disappearance of the scaffold and good integration into the host. Although control animals developed significant LV dilatation accompanied by progressive deterioration in LV contractility, in the biograft-treated rats, attenuation of LV dilatation and no change in LV contractility were observed. Conclusions —Alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells. After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls. This strategy can be used for regeneration and healing of the infarcted myocardium.

Tough Double-Network Hydrogels as Scaffolds for Tissue Engineering

2012 ◽  
pp. 213-222
Author(s):  
Jing Jing Yang ◽  
Jian Fang Liu ◽  
Takayuki Kurokawa ◽  
Nobuto Kitamura ◽  
Kazunori Yasuda ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Embryoid Bodies ◽  
Living Tissue ◽  
Double Network ◽  
Dimensional Network

Hydrogels are used as scaffolds for tissue engineering in vitro & in vivo because their three-dimensional network structure and viscoelasticity are similar to those of the macromolecular-based extracellular matrix (ECM) in living tissue. Especially, the synthetic hydrogels with controllable and reproducible properties were used as scaffolds to study the behaviors of cells in vitro and implanted test in vivo. In this review, two different structurally designed hydrogels, single-network (SN) hydrogels and double-network (DN) hydrogels, were used as scaffolds. The behavior of two cell types, anchorage-dependent cells and anchorage-independent cells, and the differentiation behaviors of embryoid bodies (EBs) were investigated on these hydrogels. Furthermore, the behavior of chondrocytes on DN hydrogels in vitro and the spontaneous cartilage regeneration induced by DN hydrogels in vivo was examined.

scholarly journals Pancreatic cancer-derived organoids – a disease modeling tool to predict drug response

2020 ◽  
Vol 8 (5) ◽  
pp. 594-606 ◽  
Author(s):  
Pierre-Olivier Frappart ◽  
Karolin Walter ◽  
Johann Gout ◽  
Alica K Beutel ◽  
Mareen Morawe ◽  
...  
Keyword(s):  
Drug Testing ◽  
Disease Modeling ◽  
Individualized Medicine ◽  
Expression Patterns ◽  
Culture Conditions ◽  
Ductal Adenocarcinoma ◽  
Small Scale ◽  
Comparative Genomic

Background Organotypic cultures derived from pancreatic ductal adenocarcinoma (PDAC) termed pancreatic ductal cancer organoids (PDOs) recapitulate the primary cancer and can be derived from primary or metastatic biopsies. Although isolation and culture of patient-derived pancreatic organoids were established several years ago, pros and cons for individualized medicine have not been comprehensively investigated to date. Methods We conducted a feasibility study, systematically comparing head-to-head patient-derived xenograft tumor (PDX) and PDX-derived organoids by rigorous immunohistochemical and molecular characterization. Subsequently, a drug testing platform was set up and validated in vivo. Patient-derived organoids were investigated as well. Results First, PDOs faithfully recapitulated the morphology and marker protein expression patterns of the PDXs. Second, quantitative proteomes from the PDX as well as from corresponding organoid cultures showed high concordance. Third, genomic alterations, as assessed by array-based comparative genomic hybridization, revealed similar results in both groups. Fourth, we established a small-scale pharmacotyping platform adjusted to operate in parallel considering potential obstacles such as culture conditions, timing, drug dosing, and interpretation of the results. In vitro predictions were successfully validated in an in vivo xenograft trial. Translational proof-of-concept is exemplified in a patient with PDAC receiving palliative chemotherapy. Conclusion Small-scale drug screening in organoids appears to be a feasible, robust and easy-to-handle disease modeling method to allow response predictions in parallel to daily clinical routine. Therefore, our fast and cost-efficient assay is a reasonable approach in a predictive clinical setting.

Sign in / Sign up

Export Citation Format

Share Document