Cardiac tissue engineering: current state-of-the-art materials, cells and tissue formation

ABSTRACT Cardiovascular diseases are the major cause of death worldwide. The heart has limited capacity of regeneration, therefore, transplantation is the only solution in some cases despite presenting many disadvantages. Tissue engineering has been considered the ideal strategy for regenerative medicine in cardiology. It is an interdisciplinary field combining many techniques that aim to maintain, regenerate or replace a tissue or organ. The main approach of cardiac tissue engineering is to create cardiac grafts, either whole heart substitutes or tissues that can be efficiently implanted in the organism, regenerating the tissue and giving rise to a fully functional heart, without causing side effects, such as immunogenicity. In this review, we systematically present and compare the techniques that have drawn the most attention in this field and that generally have focused on four important issues: the scaffold material selection, the scaffold material production, cellular selection and in vitro cell culture. Many studies used several techniques that are herein presented, including biopolymers, decellularization and bioreactors, and made significant advances, either seeking a graft or an entire bioartificial heart. However, much work remains to better understand and improve existing techniques, to develop robust, efficient and efficacious methods.

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

Micromachines ◽

10.3390/mi12040386 ◽

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.

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Vascularisation for cardiac tissue engineering: the extracellular matrix

Thrombosis and Haemostasis ◽

10.1160/th14-05-0480 ◽

2015 ◽

Vol 113 (03) ◽

pp. 532-547 ◽

Cited By ~ 15

Author(s):

Chinmoy Patra ◽

Aldo Boccaccini ◽

Felix Engel

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Cardiac Tissue ◽

Heart Diseases ◽

Cardiac Tissue Engineering ◽

Promising Candidate ◽

Realistic Option ◽

Extracellular Matrix Molecules ◽

Heart Muscle Cells

SummaryCardiovascular diseases present a major socio-economic burden. One major problem underlying most cardiovascular and congenital heart diseases is the irreversible loss of contractile heart muscle cells, the cardiomyocytes. To reverse damage incurred by myocardial infarction or by surgical correction of cardiac malformations, the loss of cardiac tissue with a thickness of a few millimetres needs to be compensated. A promising approach to this issue is cardiac tissue engineering. In this review we focus on the problem of in vitro vascularisation as implantation of cardiac patches consisting of more than three layers of cardiomyocytes (> 100 μm thick) already results in necrosis. We explain the need for vascularisation and elaborate on the importance to include non-myocytes in order to generate functional vascularised cardiac tissue. We discuss the potential of extracellular matrix molecules in promoting vascularisation and introduce nephronectin as an example of a new promising candidate. Finally, we discuss current biomaterial- based approaches including micropatterning, electrospinning, 3D micro-manufacturing technology and porogens. Collectively, the current literature supports the notion that cardiac tissue engineering is a realistic option for future treatment of paediatric and adult patients with cardiac disease.

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Chitosan as Functional Biomaterial for Designing Delivery Systems in Cardiac Therapies

Gels ◽

10.3390/gels7040253 ◽

2021 ◽

Vol 7 (4) ◽

pp. 253

Author(s):

Bhaumik Patel ◽

Ravi Manne ◽

Devang B. Patel ◽

Shashank Gorityala ◽

Arunkumar Palaniappan ◽

...

Keyword(s):

Myocardial Infarction ◽

Tissue Engineering ◽

Stem Cells ◽

Cardiac Tissue ◽

Mechanical Stability ◽

Cardiac Tissue Engineering ◽

Delivery Systems ◽

Pharmaceutical Industries

Cardiovascular diseases are a leading cause of mortality across the globe, and transplant surgeries are not always successful since it is not always possible to replace most of the damaged heart tissues, for example in myocardial infarction. Chitosan, a natural polysaccharide, is an important biomaterial for many biomedical and pharmaceutical industries. Based on the origin, degree of deacetylation, structure, and biological functions, chitosan has emerged for vital tissue engineering applications. Recent studies reported that chitosan coupled with innovative technologies helped to load or deliver drugs or stem cells to repair the damaged heart tissue not just in a myocardial infarction but even in other cardiac therapies. Herein, we outlined the latest advances in cardiac tissue engineering mediated by chitosan overcoming the barriers in cardiac diseases. We reviewed in vitro and in vivo data reported dealing with drug delivery systems, scaffolds, or carriers fabricated using chitosan for stem cell therapy essential in cardiac tissue engineering. This comprehensive review also summarizes the properties of chitosan as a biomaterial substrate having sufficient mechanical stability that can stimulate the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.

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Adipose-derived mesenchymal stem cell seeded Atelocollagen scaffolds for cardiac tissue engineering

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-020-06425-2 ◽

2020 ◽

Vol 31 (10) ◽

Author(s):

Qiong Li ◽

Miaomiao Li ◽

Meng Li ◽

Zhengyan Zhang ◽

Han Ma ◽

...

Keyword(s):

Tissue Engineering ◽

Adipose Tissue ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Subcutaneous Adipose Tissue ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Good Biocompatibility ◽

Subcutaneous Adipose

Abstract ADMSCs were isolated from subcutaneous adipose tissue, characterized and cultured in vitro. GFP-labeled ADMSCs can grow and proliferate well on the Atelocollagen scaffolds, and induced by 5-aza the cells can differentiate into cardio-like cells. 3D cultured ADMSCs on Atelocollagen scaffolds were transplanted into mice ischemia myocardium, and have good biocompatibility with host cardio tissue.

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Cardiomyocytes In Vitro Adhesion Is Actively Influenced by Biomimetic Synthetic Peptides for Cardiac Tissue Engineering

Tissue Engineering Part A ◽

10.1089/ten.tea.2011.0254 ◽

2012 ◽

Vol 18 (7-8) ◽

pp. 725-736 ◽

Cited By ~ 11

Author(s):

Alessandro Gandaglia ◽

Rocio Huerta-Cantillo ◽

Marina Comisso ◽

Roberta Danesin ◽

Francesca Ghezzo ◽

...

Keyword(s):

Tissue Engineering ◽

Synthetic Peptides ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

In Vitro Adhesion

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Cardiac tissue engineering

Journal of the Serbian Chemical Society ◽

10.2298/jsc0503541r ◽

2005 ◽

Vol 70 (3) ◽

pp. 541-556 ◽

Cited By ~ 30

Author(s):

Milica Radisic ◽

Gordana Vunjak-Novakovic

Keyword(s):

Tissue Engineering ◽

Electrical Stimulation ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Peripheral Region ◽

Heart Cells ◽

Coupled Cells ◽

Continuous Application ◽

Rat Heart Cells

We hypothesized that clinically sized (1-5 mm thick),compact cardiac constructs containing physiologically high density of viable cells (?108 cells/cm3) can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of per fluorocarbons), or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz). Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of per fluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a?100 ?m thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart) as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

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Cardiac tissue engineering: current state and perspectives

Frontiers in Bioscience ◽

10.2741/4002 ◽

2012 ◽

Vol 17 (1) ◽

pp. 1533 ◽

Cited By ~ 33

Author(s):

Loraine L., Y. Chiu

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Current State

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Abstract 181: Human Heart Valve-derived Scaffold Improves Cardiac Repair in a Murine Model of Myocardial Infarction

Circulation Research ◽

10.1161/res.117.suppl_1.181 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Jun Li ◽

Long Wan ◽

Yao Chen ◽

Zhenhua Wang ◽

Wentian Zhang ◽

...

Keyword(s):

Myocardial Infarction ◽

Tissue Engineering ◽

Heart Valve ◽

Murine Model ◽

Human Heart ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Repair ◽

Infarcted Heart

Cardiac tissue engineering using biomaterials with or without a combination of cardiac stem cell therapy offers a new therapeutic option for repairing infarcted heart. So far, cardiac tissue scaffold is designed mainly based on natural and synthetic biomaterials, which do not mimic human myocardial extracellular matrix. This raises a fundamental issue about the biocompatibility of currently used biomaterials with myocardial tissue. Here we hypothesized that human heart valve-derived scaffold (hHVS) may provide a clinically relevant novel biomaterial for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function, as shown by transthoracic echocardiography as well as by hemodynamic measurements via a Millar catheter, and by reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first evidence for translating the hHVS-based cardiac tissue engineering into clinical strategies to treat myocardial infarction.

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Abstract P403: Three-dimensional Bioprinting Of Adhesive Cardiac Patch Systems

Circulation Research ◽

10.1161/res.129.suppl_1.p403 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Shuai Chen ◽

Martin Tomov ◽

Liqun Ning ◽

Carmen Gil ◽

Boeun Hwang ◽

...

Keyword(s):

Tissue Engineering ◽

Adhesion Strength ◽

Cardiac Tissue ◽

Ex Vivo ◽

Cardiac Tissue Engineering ◽

Aqueous Environment ◽

Adhesive Properties ◽

Adhesion Properties ◽

Fidelity Assessment

Rapid advancements in 3D bioprinting have enabled the design of functionalized bioinks to create scaffolds with robust adhesive properties. These constructs are of great interest in cardiac tissue engineering, where the integration of grafted patch with the host myocardium, through sutures, staples, or adhesives, faces risks such as bleeding, cytotoxicity, and infection. We introduce the first generation of functional adhesive bioinks that can be bioprinted through various modalities to fabricate patch structures with intrinsic adhesive properties. A dopamine-modified hyaluronic acid methacrylate (HAMA-Dopa) and gelatin methacrylate (gelMA) composite bioink is used to create the patch via air and embedded bioprinting. Constructs are crosslinked onto a collagen sheet substrate simulating the host cardiac tissue ( Figure 1A-C ). We developed novel in vitro methods to assess adhesion properties of printed patch under shear, tension, or dynamic loading ( Figure 1C ). Our approach allowed for steady and precise application of stress to the adhesion interface. Embedded-printed HAMA-Dopa/gelMA scaffold showed significantly enhanced adhesion strength (1025 Pa) compared to gelMA (495 Pa) and HAMA (477 Pa) control groups under tension, and under shear (548 Pa vs. 234 and 239 Pa). The adhesion strength of air-printed HAMA-Dopa/gelMA constructs was markedly higher (10,128 Pa) than the embedded ones, possibly due to the more effective, in-situ crosslinking. We also investigated the dynamic adhesive properties in aqueous environment using an ex vivo beating heart model. Air-printed HAMA-Dopa/gelMA showed the greatest adhesion under wet conditions, tolerating 345,600 cycles. We further characterized printing fidelity, mechanical properties, swelling, and biocompatibility of HAMA-Dopa/gelMA constructs, demonstrating adequate functionality of this bioprinted adhesive scaffold for cardiac tissue engineering applications. Figure 1 . Summary of workflow to develop bioprinted adhesive scaffolds. A: Embedded (top) or air (bottom) bioprinting was used to create 3D patch geometries. B: Printing fidelity assessment and optimization. C: Different adhesion mechanisms were assessed using novel customized tools and approaches to apply tensile ( C-i ), shear ( C-ii ), and dynamic ( C-iii ) loading.

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