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Engineered myocardium

Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUNDS: -Tissue engineering enables the generation of functional human cardiac tissue using cells derived in vitro in combination with biocompatible materials. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electrical pacing on the maturation of hiPSC-derived cardiac tissues. METHODSS: -Cardiomyocytes derived from hiPSCs were used to generate collagen-based bioengineered human cardiac tissue...
October 13, 2016: Circulation
Christopher B Rodell, Madonna E Lee, Hua Wang, Satoshi Takebayashi, Tetsushi Takayama, Tomonori Kawamura, Jeffrey S Arkles, Neville N Dusaj, Shauna M Dorsey, Walter R T Witschey, James J Pilla, Joseph H Gorman, Jonathan F Wenk, Jason A Burdick, Robert C Gorman
BACKGROUND: Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements. METHODS AND RESULTS: We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel...
October 2016: Circulation. Cardiovascular Interventions
Christopher P Jackman, Aaron L Carlson, Nenad Bursac
Engineered cardiac tissues hold promise for cell therapy and drug development, but exhibit inadequate function and maturity. In this study, we sought to significantly improve the function and maturation of rat and human engineered cardiac tissues. We developed dynamic, free-floating culture conditions for engineering "cardiobundles", 3-dimensional cylindrical tissues made from neonatal rat cardiomyocytes or human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) embedded in fibrin-based hydrogel. Compared to static culture, 2-week dynamic culture of neonatal rat cardiobundles significantly increased expression of sarcomeric proteins, cardiomyocyte size (∼2...
December 2016: Biomaterials
Yu Shrike Zhang, Andrea Arneri, Simone Bersini, Su-Ryon Shin, Kai Zhu, Zahra Goli-Malekabadi, Julio Aleman, Cristina Colosi, Fabio Busignani, Valeria Dell'Erba, Colin Bishop, Thomas Shupe, Danilo Demarchi, Matteo Moretti, Marco Rasponi, Mehmet Remzi Dokmeci, Anthony Atala, Ali Khademhosseini
Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium...
December 2016: Biomaterials
Aida Llucià-Valldeperas, Carolina Soler-Botija, Carolina Gálvez-Montón, Santiago Roura, Cristina Prat-Vidal, Isaac Perea-Gil, Benjamin Sanchez, Ramon Bragos, Gordana Vunjak-Novakovic, Antoni Bayes-Genis
: : Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time...
September 29, 2016: Stem Cells Translational Medicine
Hidetoshi Masumoto, Jun K Yamashita
Stem cell therapy is a promising therapeutic option for severe cardiac diseases that are resistant to conventional therapies. To overcome the unsatisfactory results of most clinical researches on stem cell injections to an injured heart, we are developing bioengineered cardiac tissue grafts using pluripotent stem cell-derived cardiomyocytes and vascular cells. We have validated the functional benefits of mouse embryonic stem cell-derived and human induced pluripotent stem cell-derived cardiac tissue sheets (CTSs) in a rat myocardial infarction model...
November 2016: Current Treatment Options in Cardiovascular Medicine
Akiko Tanaka, Keigo Kawaji, Amit R Patel, Takeyoshi Ota
OBJECTIVES: An extracellular matrix patch was implanted in the porcine right ventricle for in situ myocardial regeneration. A newly developed cardiovascular magnetic resonance protocol was utilized to investigate the regional physio-mechanical function of the patch. METHODS: Cardiovascular magnetic resonance was performed at 60-day after the porcine right ventricular wall full thickness substitution with an extracellular matrix cardiac patch (n = 5). Dacron patches and remote normal right ventricle served as control (n = 5/each)...
September 13, 2016: Interactive Cardiovascular and Thoracic Surgery
Jonas Schwan, Andrea T Kwaczala, Thomas J Ryan, Oscar Bartulos, Yongming Ren, Lorenzo R Sewanan, Aaron H Morris, Daniel L Jacoby, Yibing Qyang, Stuart G Campbell
We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized, and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21...
2016: Scientific Reports
Michael Regn, Bernhard Laggerbauer, Claudia Jentzsch, Deepak Ramanujam, Andrea Ahles, Sonja Sichler, Julia Calzada-Wack, Rory Koenen, Attila Braun, Bernhard Nieswandt, Stefan Engelhardt
A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol-(GPI) membrane anchor...
August 15, 2016: Journal of Molecular and Cellular Cardiology
Morteza Mahmoudi, Mingming Zhao, Yuka Matsuura, Sophie Laurent, Phillip C Yang, Daniel Bernstein, Pilar Ruiz-Lozano, Vahid Serpooshan
Tissue engineering utilizes porous scaffolds as template to guide the new tissue growth. Clinical application of scaffolding biomaterials is hindered by implant-associated infection and impaired in vivo visibility of construct in biomedical imaging modalities. We recently demonstrated the use of a bioengineered type I collagen patch to repair damaged myocardium. By incorporating superparamagnetic iron oxide nanoparticles into this patch, here, we developed an MRI-visible scaffold. Moreover, the embedded nanoparticles impeded the growth of Salmonella bacteria in the patch...
2016: BioImpacts: BI
Stefano Boccardo, Emanuele Gaudiello, Ludovic Melly, Giulia Cerino, Davide Ricci, Ivan Martin, Friedrich Eckstein, Andrea Banfi, Anna Marsano
UNLABELLED: Therapeutic over-expression of Vascular Endothelial Growth Factor (VEGF) by transduced progenitors is a promising strategy to efficiently induce angiogenesis in ischemic tissues (e.g. limb muscle and myocardium), but tight control over the micro-environmental distribution of the dose is required to avoid induction of angioma-like tumors. Therapeutic VEGF release was achieved by purified transduced adipose mesenchymal stromal cells (ASC) that homogeneously produce specific VEGF levels, inducing only normal angiogenesis after injection in non-ischemic tissues...
September 15, 2016: Acta Biomaterialia
Hidetoshi Masumoto, Takeichiro Nakane, Joseph P Tinney, Fangping Yuan, Fei Ye, William J Kowalski, Kenji Minakata, Ryuzo Sakata, Jun K Yamashita, Bradley B Keller
Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs...
2016: Scientific Reports
Mahshid Kharaziha, Adnan Memic, Mohsen Akbari, David A Brafman, Mehdi Nikkhah
On page 1533 M. Nikkhah and co-workers review tissue engineering strategies in the treatment of cardiac diseases with emphasis on the use of nanoenabled approaches (e.g. nanoparticles, nanotopographies) in combination with stem cells for regeneration and repair of injured myocardium upon myocardial infarction.
July 2016: Advanced Healthcare Materials
Benjamin Kappler, Petra Anic, Matthias Becker, Andreas Bader, Kristin Klose, Oliver Klein, Barbara Oberwallner, Yeong-Hoon Choi, Volkmar Falk, Christof Stamm
Freshly isolated human cardiac extracellular matrix sheets (cECM) have been shown to support stem cell proliferation and tissue-specific lineage commitment. We now developed a protocol for standardized production of durable, bio-functional hcECM microparticles and corresponding hydrogel, and tested its cytoprotective effects on contractile cells subjected to ischemia-like conditions. Human ventricular myocardium was decellularized by a 3-step protocol, including Tris/EDTA, SDS and serum incubation (cECM). Following snap-freezing and lyophilization, microparticles were created and characterized by laser diffraction, dynamic image analysis (DIA), and mass spectrometry...
July 2016: Journal of Materials Science. Materials in Medicine
Maribella Domenech, Liliana Polo, Jaime Ramirez-Vick, Donald O Freytes
Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart...
June 7, 2016: Tissue Engineering. Part B, Reviews
Joseph J Kim, Luqia Hou, Ngan F Huang
UNLABELLED: Engineering of three-dimensional (3D) tissues is a promising approach for restoring diseased or dysfunctional myocardium with a functional replacement. However, a major bottleneck in this field is the lack of efficient vascularization strategies, because tissue constructs produced in vitro require a constant flow of oxygen and nutrients to maintain viability and functionality. Compared to angiogenic cell therapy and growth factor treatment, bioengineering approaches such as spatial micropatterning, integration of sacrificial materials, tissue decellularization, and 3D bioprinting enable the generation of more precisely controllable neovessel formation...
September 1, 2016: Acta Biomaterialia
Josue Chery, Joshua Wong, Shan Huang, Shuyun Wang, Ming-Sing Si
Hypoplastic left heart syndrome (HLHS), the most severe and common form of single ventricle congenital heart lesions, is characterized by hypoplasia of the mitral valve, left ventricle (LV), and all LV outflow structures. While advances in surgical technique and medical management have allowed survival into adulthood, HLHS patients have severe morbidities, decreased quality of life, and a shortened lifespan. The single right ventricle (RV) is especially prone to early failure because of its vulnerability to chronic pressure overload, a mode of failure distinct from ischemic cardiomyopathy encountered in acquired heart disease...
June 28, 2016: Tissue Engineering. Part B, Reviews
A Totaro, F Urciuolo, G Imparato, P A Netti
The in vitro fabrication of an endogenous cardiac muscle would have a high impact for both in vitro studies concerning cardiac tissue physiology and pathology, as well as in vivo application to potentially repair infarcted myocardium. To reach this aim, we engineered a new class of cardiac tissue precursor (CTP), specifically conceived in order to promote the synthesis and the assembly of a cardiac extracellular matrix (ECM). The CTPs were obtained by culturing a mixed cardiac cell population, composed of myocyte and non-myocyte cells, into porous gelatin microspheres in a dynamic bioreactor...
June 2016: Biofabrication
Mahshid Kharaziha, Adnan Memic, Mohsen Akbari, David A Brafman, Mehdi Nikkhah
Cardiac diseases are the most prevalent causes of mortality in the world, putting a major economic burden on global healthcare system. Tissue engineering strategies aim at developing efficient therapeutic approaches to overcome the current challenges in prolonging patients survival upon cardiac diseases. The integration of advanced biomaterials and stem cells has offered enormous promises for regeneration of damaged myocardium. Natural or synthetic biomaterials have been extensively used to deliver cells or bioactive molecules to the site of injury in heart...
July 2016: Advanced Healthcare Materials
Rajesh Lakshmanan, Priyadharshini Kumaraswamy, Uma Maheswari Krishnan, Swaminathan Sethuraman
The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning...
August 2016: Biomaterials
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