Article
Engineering, Biomedical
Nathaniel Huebsch, Berenice Charrez, Gabriel Neiman, Brian Siemons, Steven C. Boggess, Samuel Wall, Verena Charwat, Karoline H. Jaeger, David Cleres, Ashild Telle, Felipe T. Lee-Montiel, Nicholas C. Jeffreys, Nikhil Deveshwar, Andrew G. Edwards, Jonathan Serrano, Matija Snuderl, Andreas Stahl, Aslak Tveito, Evan W. Miller, Kevin E. Healy
Summary: Mechanical stimuli and metabolic cues can enhance the maturation of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs), resulting in phenotype-dependent effects on action-potential morphology and calcium handling.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Ece Ergir, Jorge Oliver-De la Cruz, Soraia Fernandes, Marco Cassani, Francesco Niro, Daniel Pereira-Sousa, Jan Vrbsky, Vladimir Vinarsky, Ana Rubina Perestrelo, Doriana Debellis, Natalia Vadovicova, Stjepan Uldrijan, Francesca Cavalieri, Stefania Pagliari, Heinz Redl, Peter Ertl, Giancarlo Forte
Summary: The study proposes a scaffold-free method to generate physiologically relevant human cardiac tissue models in vitro. These models exhibit self-organization, long-term culture ability, and contain multiple cell types and functional cardiac properties, making them a powerful platform for translational research in cardiovascular biology.
SCIENTIFIC REPORTS
(2022)
Article
Biophysics
Xiao-Pei Li, Kai-Yun Qu, Bin Zhou, Feng Zhang, Yin-Ying Wang, Oluwatosin David Abodunrin, Zhen Zhu, Ning-Ping Huang
Summary: The study demonstrated that the combination of GelMA-PDA-rGO based conductive hydrogels and electrical stimulation had synergistic effects, which could be used for engineering a more functional and mature myocardium layer, as well as for further application in drug screening and disease modeling in vitro.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Biophysics
Abdullah-Bin Siddique, Arunkumar Shanmugasundaram, Jong Yun Kim, Amir Roshanzadeh, Eung-Sam Kim, Bong-Kee Lee, Dong-Weon Lee
Summary: Due to their immature morphology and functional immaturity, cardiomyocytes have limited use as an in vitro disease model of the native heart. Mechanical stimulation and nano-groove patterns have been found to promote structural development and contractile activity in cardiomyocytes. The stretching mechanisms of the circular diaphragm may contribute to the formation of natural myocardium.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biology
Matthew J. Powell-Palm, Verena Charwat, Berenice Charrez, Brian Siemons, Kevin E. Healy, Boris Rubinsky
Summary: The study demonstrates the preservation and revival of autonomously beating, 3D human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues at sub-zero centigrade through isochoric supercooling, without the use of chemical cryoprotectants. It suggests that functional 3D engineered tissues could serve as a valuable testbed for studying complex tissue biopreservation in a genetically human context, and that isochoric supercooling may offer a robust method for preserving and reviving engineered tissues.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biophysics
Wenkun Dou, Li Wang, Manpreet Malhi, Haijiao Liu, Qili Zhao, Julia Plakhotnik, Zhensong Xu, Zongjie Huang, Craig A. Simmons, Jason T. Maynes, Yu Sun
Summary: The study developed a microdevice platform that applied cyclical strains of varying magnitudes to iPSC-CMs and measured contractile stress using fluorescent nanobeads. It was found that cyclic strain induced cell alignment and gradually increased contractile force of iPSC-CMs over a 10-day culture period. Contractility positively correlated with sarcomere elongation and increased MYH7 expression in a strain magnitude-dependent manner, indicating mechanical stress optimization for cellular maturation.
BIOSENSORS & BIOELECTRONICS
(2021)
Review
Cell & Tissue Engineering
Kayla Soon, Omar Mourad, Sara S. Nunes
Summary: Recent advances in stem cell biology, materials science, and engineering have enabled rapid progress in cardiac tissue engineering, allowing the development of more accurate functional 3D cardiac microtissues from human cell sources. These engineered tissues have various applications, including cardiotoxic drug screening, disease modeling, and novel drug development platforms.
Article
Cardiac & Cardiovascular Systems
Shoshana L. Das, Bryan P. Sutherland, Emma Lejeune, Jeroen Eyckmans, Christopher S. Chen
Summary: In this study, an in vitro cardiac microtissue injury system was developed to mimic the regional responses seen after myocardial infarction. The injured region showed a complete loss of contractile function, while the uninjured regions exhibited elevated contractile function, compensating for the loss of function in the injured region. This work provides a new in vitro model for studying cardiac tissue remodeling and electromechanical changes after injury.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Chemistry, Analytical
Yabei Li, Zhaoyang Ye, Junjie Zhang, Yuxiang Zhao, Tong Zhu, Jingjing Song, Feng Xu, Fei Li
Summary: The in vitro cardiac tissue model is a promising platform for drug screening, with key parameters such as respiratory activity, contraction frequency, and extracellular H2O2 levels. Using SECM technology, the study monitored the dynamic changes in cardiac tissue in real-time, revealing different effects of isoproterenol and propranolol treatment on cardiac tissues.
ANALYTICAL CHEMISTRY
(2022)
Article
Engineering, Manufacturing
Chenyan Wang, Zacharias Vangelatos, Tackla Winston, Shiyang Sun, Costas P. Grigoropoulos, Zhen Ma
Summary: Researching the interaction between mechanical metamaterials and living tissues at a microstructural level is crucial for the development of advanced medical implants. By utilizing human induced pluripotent stem cell technology and multiphoton lithography, an in vitro microtissue model was established. Different unit geometries of metamaterial scaffolds can influence cellular behavior and tissue integration.
3D PRINTING AND ADDITIVE MANUFACTURING
(2022)
Article
Multidisciplinary Sciences
Xiang Wang, Qiang Gao, Xiaoning Han, Bing Bu, Longfei Wang, Aoqi Li, Linhong Deng
Summary: Mechanical forces generated by cells and tension of the extracellular matrix play a crucial role in tissue morphology. A new method using highly stretchable polymer-based microstrings was developed to detect cell-derived forces during tissue densification, revealing the interaction between cells and ECM in soft tissue densification.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Jasmeet S. Reyat, Alessandro di Maio, Beata Grygielska, Jeremy Pike, Samuel Kemble, Antonio Rodriguez-Romero, Christina Simoglou Karali, Adam P. Croft, Bethan Psaila, Filipa Simoes, Julie Rayes, Abdullah O. Khan
Summary: This work presents a novel method for generating chamber-specific cardiac microtissues that enable multi-parametric assessment of cardiac remodeling and drug screening. The microtissues showed robust vascular system and exhibited similarities to in vivo-derived anatomical cardiac tissues. Pro-fibrotic stimulation led to hallmarks of cardiac fibrosis in the microtissues, which could be reversed by specific inhibitors.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Mao Mao, Xiaoli Qu, Yabo Zhang, Bingsong Gu, Chen Li, Rongzhi Liu, Xiao Li, Hui Zhu, Jiankang He, Dichen Li
Summary: The authors developed a leaf-venation-directed strategy to engineer cardiac tissues with tissue-like properties. This strategy enables the compaction and remodeling of cell-hydrogel hybrids into aligned and densely packed organizations, resulting in advanced maturation and functionality of cardiac tissues.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Zuwan Lin, Jessica C. Garbern, Ren Liu, Qiang Li, Estela Mancheno Juncosa, Hannah L. T. Elwell, Morgan Sokol, Junya Aoyama, Undine-Sophie Deumer, Emma Hsiao, Hao Sheng, Richard T. Lee, Jia Liu
Summary: The electrical integration of transplanted cardiomyocytes is crucial for the clinical application of stem cell therapies in heart disease. In this study, researchers found that endothelial cells derived from induced pluripotent stem cells (hiPSC-ECs) promoted the maturation of hiPSC-derived cardiomyocytes (hiPSC-CMs) in terms of electrical activity. By using advanced nanoelectronics, they were able to map the electrical activity of three-dimensional cardiac microtissues, revealing that hiPSC-ECs accelerated the electrical maturation of hiPSC-CMs. Furthermore, single-cell RNA sequencing and machine learning-based analysis provided insights into the molecular mechanisms underlying hiPSC-CM electrical maturation, showing that hiPSC-ECs play a key role in this process.
Article
Engineering, Environmental
Yanping Zhang, Alice Le Friec, Di Sun, Menglin Chen
Summary: The development of flexible electronics with adjustable performance offers a promising approach for treating cardiac diseases, overcoming the limitations of conventional electronic systems due to biomechanical mismatches. By exploring the natural flow behavior of polymer melt in Melt electrowriting (MEW), researchers created a fibrous mesh electrode with a sinusoidal anisotropic structure resembling the collagen fiber architecture in the heart. This anisotropic, stretchable electrode mesh demonstrated the ability to synchronize cardiomyocyte beating through its biomimetic viscoelastic behavior and fine-tuned electrical properties, offering great potential for cardiac repair.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Engineering, Biomedical
Roberta Visone, Giovanni S. Ugolini, Daniela Cruz-Moreira, Simona Marzorati, Stefano Piazza, Enrico Pesenti, Alberto Redaelli, Matteo Moretti, Paola Occhetta, Marco Rasponi
Summary: Cardiac toxicity is a common adverse outcome in drug development that can lead to withdrawal of drugs from the market. Recent advancements in developing in vitro models resembling the human heart have allowed for more accurate detection of drug-induced cardiac toxicity early in the drug development process. Organs-on-chip are considered promising tools to replicate key aspects of in vivo cardiac physiology and provide a means for direct analysis of functional outputs.
Article
Biotechnology & Applied Microbiology
Daniela Cruz-Moreira, Roberta Visone, Francisco Vasques-Novoa, Antonio S. Barros, Adelino Leite-Moreira, Alberto Redaelli, Matteo Moretti, Marco Rasponi
Summary: Heart-on-chip technology can recapitulate key signals in cardiac pathophysiology, and the new platform allows precise fluid control to improve microtissue performance. Different flow patterns impact the structure and gene expression of microtissues.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Engineering, Biomedical
Carlotta Mondadori, Silvia Palombella, Shima Salehi, Giuseppe Talo, Roberta Visone, Marco Rasponi, Alberto Redaelli, Valerio Sansone, Matteo Moretti, Silvia Lopa
Summary: This study developed an organotypic microfluidic model to recapitulate the pathological process of the synovium in osteoarthritis patients. The model demonstrated that OA synovial fluid induces monocytes to cross the endothelium and invade the synovial compartment, and the simultaneous blocking of CCR2 and CCR5 pathways is more effective in inhibiting extravasation.
Article
Engineering, Biomedical
Kristina Haase, Filippo Piatti, Minerva Marcano, Yoojin Shin, Roberta Visone, Alberto Redaelli, Marco Rasponi, Roger D. Kamm
Summary: Hemodynamics is crucial for the health and disease of blood vessels. Microfluidic technologies have been used to develop 3D vascular models for studying human vessels. The study found that interstitial flow enhances early vessel formation, while continuous flow maintains stable vessels and causes remodeling. Flow-conditioned vessels have improved barrier function and reduced harmful substances.
Article
Engineering, Biomedical
Sandra Camarero-Espinosa, Maria Carlos-Oliveira, Hong Liu, Joao F. Mano, Nicole Bouvy, Lorenzo Moroni
Summary: The research investigates the immunomodulatory properties of dual-porosity scaffolds with varying mechanical and topographical features, demonstrating the significant impact of the interplay between scaffold stiffness and surface properties on immune response and healing processes.
ADVANCED HEALTHCARE MATERIALS
(2022)
Correction
Biophysics
Maria Carlos-Oliveira, Ferran Lozano-Juan, Paola Occhetta, Roberta Visone, Marco Rasponi
BIOPHYSICAL REVIEWS
(2022)
Article
Toxicology
Roberta Visone, Ferran Lozano-Juan, Simona Marzorati, Massimo Walter Rivolta, Enrico Pesenti, Alberto Redaelli, Roberto Sassi, Marco Rasponi, Paola Occhetta
Summary: Determining the potential cardiotoxicity and pro-arrhythmic effects of drug candidates is crucial in drug development. This study investigates the use of uHeart, a 3D miniaturized in vitro model of human myocardium, to evaluate drug-induced QT alterations and arrhythmic events. The results show that uHeart is capable of accurately predicting clinical outcomes and detecting cardiotoxic drug concentrations, making it a promising preclinical tool for cardiotoxicity studies.
TOXICOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pietro Giuseppe Mazzara, Elena Criscuolo, Marco Rasponi, Luca Massimino, Sharon Muggeo, Cecilia Palma, Matteo Castelli, Massimo Clementi, Roberto Burioni, Nicasio Mancini, Vania Broccoli, Nicola Clementi
Summary: This study has developed a stable and reliable in vitro system that models the connectivity between different human sensory neurons and peripheral tissues. By analyzing the infection process of herpes simplex virus 1 (HSV-1), it provides a better understanding of viral latency and reactivation at the cellular and molecular levels.
Article
Biochemical Research Methods
Giovanni Protopapa, Nina Bono, Roberta Visone, Fabio D'Alessandro, Marco Rasponi, Gabriele Candiani
Summary: This study developed a microfluidic cartridge for the preparation of non-viral gene delivery complexes at different N/Ps, allowing for the simultaneous generation of multiple polymer-to-NA ratios. The cartridge offers advantages in terms of speed and repeatability, making it a user-friendly tool in transfection research.
Article
Materials Science, Multidisciplinary
Erika Ferrari, Roberta Visone, Elisa Monti, Enrica Torretta, Matteo Moretti, Paola Occhetta, Marco Rasponi
Summary: The drug discovery and development process is long, expensive, and risky. Undetected toxicity is the primary reason for drug attrition, especially hepatic and cardiac toxicities which lead to safety-related drug withdrawals. Multi Organs-on-Chip (MOoC) is an innovative solution that enables simultaneous assessment of drug effects on multiple organs and efficient prediction of drug toxicity in preclinical trials. By focusing on drug safety, a versatile MOoC platform with two culture chambers is developed, facilitating communication between a metabolically competent liver model and a functional 3D heart model. Through the administration of Terfenadine, it is shown that liver metabolism and controlled drug diffusion are essential for inducing a physiopathological cardiac response, leading to the development of an optimized LivHeart platform that accurately predicts Terfenadine's off-target cardiotoxicity after liver metabolism.
ADVANCED MATERIALS TECHNOLOGIES
(2023)
Article
Multidisciplinary Sciences
Chiara Mancino, Anna Pasto, Enrica De Rosa, Luigi Dolcetti, Marco Rasponi, Patrick McCulloch, Francesca Taraballi
Summary: Post-traumatic osteoarthritis (PTOA) is a major cause of disability in developed countries, accounting for 12% of all osteoarthritis cases in the United States. Current therapeutic strategies are ineffective, and PTOA remains a clinical challenge. This study evaluates the targeting potential of liposome-based nanoparticles (NPs) in a PTOA mouse model during the acute phase of inflammation. The results show preferential accumulation of NPs within the injured joint, as well as an immunomodulatory effect reducing immune cell infiltration.
Article
Engineering, Biomedical
Roberta Visone, Camilla Paoletti, Alessandro Cordiale, Letizia Nicoletti, Carla Divieto, Marco Rasponi, Valeria Chiono, Paola Occhetta
Summary: Cardiac fibrosis is a major cause of heart failure, and finding effective therapies is crucial. Researchers developed a 3D in vitro model called uScar by applying mechanical stimulation to human cardiac fibroblasts. This model was used to screen drugs and advanced therapeutics. The mechanical stimulation induced fibrotic traits, which could be prevented by anti-fibrotic drugs. However, a miRNA therapy showed limitations in reprogramming fibroblasts into cardiomyocytes. Incorporating in vivo-like stimulation in 3D models is important to predict therapy efficacy in patients.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Biochemical Research Methods
Andrea Mainardi, Francesca Carminati, Giovanni Stefano Ugolini, Paola Occhetta, Giuseppe Isu, Diana Robles Diaz, Gregory Reid, Roberta Visone, Marco Rasponi, Anna Marsano
Summary: Cardiac fibrosis is a maladaptive remodeling of the myocardium characterized by impairment in contraction and excessive ECM deposition. Traditional in vitro models for studying fibrosis often overlook key factors, prompting researchers to develop a micro-physiological system for high-throughput studies in a relevant, mechanically active environment.