3D bioprinted and integrated platforms for cardiac tissue modeling and drug testing

2021 ◽  
Author(s):  
Uijung Yong ◽  
Byeongmin Kang ◽  
Jinah Jang

Abstract Recent advances in biofabrication techniques, including 3D bioprinting, have allowed for the fabrication of cardiac models that are similar to the human heart in terms of their structure (e.g., volumetric scale and anatomy) and function (e.g., contractile and electrical properties). The importance of developing techniques for assessing the characteristics of 3D cardiac substitutes in real time without damaging their structures has also been emphasized. In particular, the heart has two primary mechanisms for transporting blood through the body: contractility and an electrical system based on intra and extracellular calcium ion exchange. This review introduces recent trends in 3D bioprinted cardiac tissues and the measurement of their structural, contractile, and electrical properties in real time. Cardiac models have also been regarded as alternatives to animal models as drug-testing platforms. Thus, perspectives on the convergence of 3D bioprinted cardiac tissues and their assessment for use in drug development are also presented.

2017 ◽  
Vol 131 (13) ◽  
pp. 1393-1404 ◽  
Author(s):  
Anastasia Korolj ◽  
Erika Yan Wang ◽  
Robert A. Civitarese ◽  
Milica Radisic

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing.


Gels ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 53
Author(s):  
Kaylee Meyers ◽  
Bruce P. Lee ◽  
Rupak M. Rajachar

Due to the limited regenerative capabilities of cardiomyocytes, incidents of myocardial infarction can cause permanent damage to native myocardium through the formation of acellular, non-conductive scar tissue during wound repair. The generation of scar tissue in the myocardium compromises the biomechanical and electrical properties of the heart which can lead to further cardiac problems including heart failure. Currently, patients suffering from cardiac failure due to scarring undergo transplantation but limited donor availability and complications (i.e., rejection or infectious pathogens) exclude many individuals from successful transplant. Polymeric tissue engineering scaffolds provide an alternative approach to restore normal myocardium structure and function after damage by acting as a provisional matrix to support cell attachment, infiltration and stem cell delivery. However, issues associated with mechanical property mismatch and the limited electrical conductivity of these constructs when compared to native myocardium reduces their clinical applicability. Therefore, composite polymeric scaffolds with conductive reinforcement components (i.e., metal, carbon, or conductive polymers) provide tunable mechanical and electroactive properties to mimic the structure and function of natural myocardium in force transmission and electrical stimulation. This review summarizes recent advancements in the design, synthesis, and implementation of electroactive polymeric composites to better match the biomechanical and electrical properties of myocardial tissue.


2021 ◽  
Vol 12 ◽  
Author(s):  
Moustafa H. Meki ◽  
Jessica M. Miller ◽  
Tamer M. A. Mohamed

Translational research in the cardiovascular field is hampered by the unavailability of cardiac models that can recapitulate organ-level physiology of the myocardium. Outside the body, cardiac tissue undergoes rapid dedifferentiation and maladaptation in culture. There is an ever-growing demand for preclinical platforms that allow for accurate, standardized, long-term, and rapid drug testing. Heart slices is an emerging technology that solves many of the problems with conventional myocardial culture systems. Heart slices are thin (<400 µm) slices of heart tissue from the adult ventricle. Several recent studies using heart slices have shown their ability to maintain the adult phenotype for prolonged periods in a multi cell-type environment. Here, we review the current status of cardiac culture systems and highlight the unique advantages offered by heart slices in the light of recent efforts in developing physiologically relevant heart slice culture systems.


2017 ◽  
Vol 114 (8) ◽  
pp. 1898-1903 ◽  
Author(s):  
Sharon Fleischer ◽  
Assaf Shapira ◽  
Ron Feiner ◽  
Tal Dvir

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 51
Author(s):  
William P. Lafuse ◽  
Daniel J. Wozniak ◽  
Murugesan V. S. Rajaram

The immune system plays a pivotal role in the initiation, development and resolution of inflammation following insult or damage to organs. The heart is a vital organ which supplies nutrients and oxygen to all parts of the body. Heart failure (HF) has been conventionally described as a disease associated with cardiac tissue damage caused by systemic inflammation, arrhythmia and conduction defects. Cardiac inflammation and subsequent tissue damage is orchestrated by the infiltration and activation of various immune cells including neutrophils, monocytes, macrophages, eosinophils, mast cells, natural killer cells, and T and B cells into the myocardium. After tissue injury, monocytes and tissue-resident macrophages undergo marked phenotypic and functional changes, and function as key regulators of tissue repair, regeneration and fibrosis. Disturbance in resident macrophage functions such as uncontrolled production of inflammatory cytokines, growth factors and inefficient generation of an anti-inflammatory response or unsuccessful communication between macrophages and epithelial and endothelial cells and fibroblasts can lead to aberrant repair, persistent injury, and HF. Therefore, in this review, we discuss the role of cardiac macrophages on cardiac inflammation, tissue repair, regeneration and fibrosis.


2015 ◽  
Vol 4 (1) ◽  
pp. 4-18
Author(s):  
Lauren Rebecca Sklaroff

This state of the field essay examines recent trends in American Cultural History, focusing on music, race and ethnicity, material culture, and the body. Expanding on key themes in articles featured in the special issue of Cultural History, the essay draws linkages to other important literatures. The essay argues for more a more serious consideration of the products within popular culture, less as a reflection of social or economic trends, rather for their own historical significance. While the essay examines some classic texts, more emphasis is on work published within the last decade. Here, interdisciplinary methods are stressed, as are new research perspectives developing by non-western historians.


2018 ◽  
Author(s):  
Anna Adams ◽  
Radha Krishna Murthy Bulusu ◽  
Nikita Mukhitov ◽  
Jose Mendoza-Cortes ◽  
Michael Roper

In this work, we developed a microfluidic bioreactor for optimizing growth and maintaining structure and function of HepG2, and when desired, the device could be removed and the extracellular output from the bioreactor combined with enzymatic glucose reagents into a droplet-based microfluidic system. The intensity of the resulting fluorescent assay product in the droplets was measured, and was directly correlated to glucose concentration, allowing the effect of insulin on glucose consumption in the HepG2 cells to be observed and quantified online and in near real-time.


2018 ◽  
Author(s):  
Anna Adams ◽  
Radha Krishna Murthy Bulusu ◽  
Nikita Mukhitov ◽  
Jose Mendoza-Cortes ◽  
Michael Roper

In this work, we developed a microfluidic bioreactor for optimizing growth and maintaining structure and function of HepG2, and when desired, the device could be removed and the extracellular output from the bioreactor combined with enzymatic glucose reagents into a droplet-based microfluidic system. The intensity of the resulting fluorescent assay product in the droplets was measured, and was directly correlated to glucose concentration, allowing the effect of insulin on glucose consumption in the HepG2 cells to be observed and quantified online and in near real-time.


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