One-Step 3D Printing of Heart Patches with Built-In Electronics for Performance Regulation.
TL;DR: One‐step 3D printing of cardiac patches with built‐in soft and stretchable electronics is reported and it is shown that the hybrid system can withstand continuous physical deformations as those taking place in the contracting myocardium.
Abstract: Three dimensional (3D) printing of heart patches usually provides the ability to precisely control cell location in 3D space. Here, one-step 3D printing of cardiac patches with built-in soft and stretchable electronics is reported. The tissue is simultaneously printed using three distinct bioinks for the cells, for the conducting parts of the electronics and for the dielectric components. It is shown that the hybrid system can withstand continuous physical deformations as those taking place in the contracting myocardium. The electronic patch is flexible, stretchable, and soft, and the electrodes within the printed patch are able to monitor the function of the engineered tissue by providing extracellular potentials. Furthermore, the system allowed controlling tissue function by providing electrical stimulation for pacing. It is envisioned that such transplantable patches may regain heart contractility and allow the physician to monitor the implant function as well as to efficiently intervene from afar when needed.
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TL;DR: The work was supported by the NNSF of China (21805136, 62174085), Jiangsu Province Policy Guidance Plan (BZ2019014), Six talent peak innovation team in Jiangsu province (TD-SWYY-009), “Taishan scholars” construction special fund of Shandong Province, and King Abdullah University of Science & Technology (KAUST) as discussed by the authors.
Abstract: The work was supported by the NNSF of China (21805136, 62174085), Jiangsu Province Policy Guidance Plan (BZ2019014), Six talent peak innovation team in Jiangsu Province (TD-SWYY-009), “Taishan scholars” construction special fund of Shandong Province, and King Abdullah University of Science & Technology (KAUST).
49 citations
TL;DR: A comprehensive review of recent advances in the additive manufacturing of micro-nano functional devices is provided in this paper , where functional materials for micro/nano AM are also summarized.
22 citations
TL;DR: A review of state-of-the-art studies, challenges that have not yet been overcome and perspectives on cardiac tissue engineering can be found in this paper, where the most clinically relevant cell sources used in this field and discuss the use of topological, biophysical and metabolic stimuli to obtain mature phenotypes of cardiomyocytes.
Abstract: Successfully engineering a functional, human, myocardial pump would represent a therapeutic alternative for the millions of patients with end-stage heart disease and provide an alternative to animal-based preclinical models. Although the field of cardiac tissue engineering has made tremendous advances, major challenges remain, which, if properly resolved, might allow the clinical implementation of engineered, functional, complex 3D structures in the future. In this Review, we provide an overview of state-of-the-art studies, challenges that have not yet been overcome and perspectives on cardiac tissue engineering. We begin with the most clinically relevant cell sources used in this field and discuss the use of topological, biophysical and metabolic stimuli to obtain mature phenotypes of cardiomyocytes, particularly in relation to organized cytoskeletal and contractile intracellular structures. We then move from the cellular level to engineering planar cardiac patches and discuss the need for proper vascularization and the main strategies for obtaining it. Finally, we provide an overview of several different approaches for the engineering of volumetric organs and organ parts - from whole-heart decellularization and recellularization to advanced 3D printing technologies.
22 citations
TL;DR: In this paper , the authors provide a timely and comprehensive review of 3D printing for the textile and fashion industries according to recent advances in research, and summarize three routes to use 3D technology in textile manufacturing, including printing fibers, printing flexible structures and printing on textiles.
Abstract: Three-dimensional printing (3DP) allows for the creation of highly complex products and offers customization for individual users. It has generated significant interest and shows great promise for textile and fashion design. Here, we provide a timely and comprehensive review of 3DP technology for the textile and fashion industries according to recent advances in research. We describe the four 3DP methods for preparing textiles; then, we summarize three routes to use 3DP technology in textile manufacturing, including printing fibers, printing flexible structures and printing on textiles. In addition, the applications of 3DP technology in fashion design, functional garments and electronic textiles are introduced. Finally, the challenges and prospects of 3DP technology are discussed.
22 citations
TL;DR: In this article , an organogel/silicone fiber-helical sensor based on a triboelectric nanogenerator (OFS-TENG) is developed for power-free and sutureable implantation ligament strain monitoring.
Abstract: Implantable sensors with the abilities of real-time healthcare monitoring and auxiliary training are important for exercise-induced or disease-induced muscle and ligament injuries. However, some of these implantable sensors have some shortcomings, such as requiring an external power supply or poor flexibility and stability. Herein, an organogel/silicone fiber-helical sensor based on a triboelectric nanogenerator (OFS-TENG) is developed for power-free and sutureable implantation ligament strain monitoring. The OFS-TENG with high stability and ultrastretchability is composed of an organogel fiber and a silicone fiber intertwined with a double helix structure. The organogel fiber possesses the merits of rapid preparation (15 s), good transparency (>95%), high stretchability (600%), and favorable stability (over 6 months). The OFS-TENG is successfully implanted on the patellar ligament of the rabbit knee for the real-time monitoring of knee ligament stretch and muscle stress, which is expected to provide a solution for real-time diagnosis of muscle and ligament injuries. The prepared self-powered OFS-TENG can monitor data on human muscles and ligaments in real-time.
14 citations
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TL;DR: The expanding range of printable materials, coupled with the ability to programmably control their composition and architecture across various length scales, is driving innovation in myriad applications.
Abstract: Light- and ink-based three-dimensional (3D) printing methods allow the rapid design and fabrication of materials without the need for expensive tooling, dies or lithographic masks. They have led to an era of manufacturing in which computers can control the fabrication of soft matter that has tunable mechanical, electrical and other functional properties. The expanding range of printable materials, coupled with the ability to programmably control their composition and architecture across various length scales, is driving innovation in myriad applications. This is illustrated by examples of biologically inspired composites, shape-morphing systems, soft sensors and robotics that only additive manufacturing can produce.
1,054 citations
TL;DR: The ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents represents a promising paradigm to study disease mechanisms, optimize patient care, and aid in the development of new therapies.
Abstract: The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death. Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.
1,011 citations
TL;DR: 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro–computed tomography and showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.
Abstract: Collagen is the primary component of the extracellular matrix in the human body. It has proved challenging to fabricate collagen scaffolds capable of replicating the structure and function of tissues and organs. We present a method to 3D-bioprint collagen using freeform reversible embedding of suspended hydrogels (FRESH) to engineer components of the human heart at various scales, from capillaries to the full organ. Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and microvascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.
996 citations
TL;DR: A simple approach to 3D‐print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported and cellularized human hearts with a natural architecture are printed.
Abstract: Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D-print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels. The ability to print functional vascularized patches according to the patient's anatomy is demonstrated. Blood vessel architecture is further improved by mathematical modeling of oxygen transfer. The structure and function of the patches are studied in vitro, and cardiac cell morphology is assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. Finally, as a proof of concept, cellularized human hearts with a natural architecture are printed. These results demonstrate the potential of the approach for engineering personalized tissues and organs, or for drug screening in an appropriate anatomical structure and patient-specific biochemical microenvironment.
635 citations
TL;DR: The binding constant of troponin for calcium is a function of developed tension and the shape of the tension‐length relation depends on the procedure used to determine it and this change in shape can be attributed to changes in activation.
Abstract: 1. The calcium-sensitive photoprotein aequorin was micro-injected into cells of rat and cat ventricular muscles. The resulting light emission is a function of intracellular free calcium concentration ([Ca2+]i). The transient increases in [Ca2+]i that accompany contraction were monitored. 2. After an increase in muscle length, the developed tension increased immediately and then showed a slow increase over a period of minutes. The peak [Ca2+]i in each contraction was initially unchanged after an increase in muscle length but then showed a slow increase with a time course similar to that of the slow tension change. 3. As a consequence of these slow changes, the shape of the tension-length relation depends on the procedure used to determine it and this change in shape can be attributed to changes in activation. 4. Immediately after an increase in muscle length the calcium transient was abbreviated. 5. When a quick release was performed during a contraction, a short-lived increase in the [Ca2+]i was observed following the release. 6. The two previous observations can both be explained if the binding constant of troponin for calcium is a function of developed tension.
559 citations