scholarly journals Designing a 3D Printing Based Auxetic Cardiac Patch with hiPSC-CMs for Heart Repair

2021 ◽  
Vol 8 (12) ◽  
pp. 172
Author(s):  
Olga Brazhkina ◽  
Jeong Hun Park ◽  
Hyun-Ji Park ◽  
Sruti Bheri ◽  
Joshua T. Maxwell ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
3D Printing ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Cells ◽  
Heart Repair ◽  
Promising Therapeutic Approach ◽  
Tunable Mechanical Properties ◽  
Induced Pluripotent ◽  
Cardiac Patch

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson’s ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease.

scholarly journals Electrospun Scaffolds and Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Engineering Applications

2020 ◽  
Vol 7 (3) ◽  
pp. 105
Author(s):  
Taylor Cook Suh ◽  
Alaowei Y. Amanah ◽  
Jessica M. Gluck
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Complex Structure ◽  
Functional Limitation ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Cells ◽  
Electrospun Scaffolds ◽  
Induced Pluripotent

Tissue engineering (TE) combines cells, scaffolds, and growth factors to assemble functional tissues for repair or replacement of tissues and organs. Cardiac TE is focused on developing cardiac cells, tissues, and structures—most notably the heart. This review presents the requirements, challenges, and research surrounding electrospun scaffolds and induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) towards applications to TE hearts. Electrospinning is an attractive fabrication method for cardiac TE scaffolds because it produces fibers that demonstrate the optimal potential for mimicking the complex structure of the cardiac extracellular matrix (ECM). iPSCs theoretically offer the capacity to generate limitless numbers of CMs for use in TE hearts, however these iPSC-CMs are electrophysiologically, morphologically, mechanically, and metabolically immature compared to adult CMs. This presents a functional limitation to their use in cardiac TE, and research aiming to address this limitation is presented in this review.

Abstract 366: Engineered Human Cardiac Tissue from Skeletal Muscle Derived Cells and Induced Pluripotent Stem Cell Derived Cardiomyocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kimimasa Tobita ◽  
Jason S Tchao ◽  
Jong Kim ◽  
Bo Lin ◽  
Johnny Huard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Troponin I ◽  
Troponin T ◽  
Induced Pluripotent Stem Cell ◽  
Human Cardiac Tissue ◽  
Induced Pluripotent ◽  
Immature Myocardium

We have previously shown that rat skeletal muscle derived stem cells differentiate into an immature cardiomyocyte (CM) phenotype within a 3-dimensional collagen gel engineered cardiac tissue (ECT). Here, we investigated whether human skeletal muscle derived progenitor cells (skMDCs) can differentiate into a CM phenotype within ECT similar to rat skeletal muscle stem cells and compared the human skMDC-ECT properties with ECT from human induced pluripotent stem cell (iPSc) derived CMs. SkMDCs differentiated into a cardiac muscle phenotype within ECT and exhibited spontaneous beating activity as early as culture day 4 and maintained their activity for more than 2 weeks. SkMDC-ECTs stained positive for cardiac specific troponin-T and troponin-I, and were co-localized with fast skeletal muscle myosin heavy chain (sk-fMHC) with a striated muscle pattern similar to fetal myocardium. The iPS-CM-ECTs maintained spontaneous beating activity for more than 2 weeks from ECT construction. iPS-CM stained positive for both cardiac troponin-T and troponin-I, and were also co-localized with sk-fMHC while the striated expression pattern of sk-fMHC was lost similar to post-natal immature myocardium. Connexin-43 protein was expressed in both engineered tissue types, and the expression pattern was similar to immature myocardium. The skMDC-ECT significantly upregulated expression of cardiac-specific genes compared to conventional 2D culture. SkMDC-ECT displayed cardiac muscle like intracellular calcium ion transients. The contractile force measurements demonstrated functional properties of fetal type myocardium in both ECTs. Our results suggest that engineered human cardiac tissue from skeletal muscle progenitor cells mimics developing fetal myocardium while the engineered cardiac tissue from inducible pluripotent stem cell-derived cardiomyocytes mimics post-natal immature myocardium.

Abstract 205: Feasibility and Testing of a Human Induced Pluripotent Stem Cell Derived Cardiac Patch in a Pre-clinical Swine Model of CHF

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jordan J Lancaster ◽  
Ike Chinyere ◽  
Bin Na Kim ◽  
Sherry Daugherty ◽  
Samuel Kim ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Dermal Fibroblasts ◽  
Swine Model ◽  
Induced Pluripotent ◽  
Cardiac Patch

Introduction: Previously we have demonstrated that a tissue engineered heart patch comprised of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and fibroblasts improves both left ventricular (LV) systolic and diastolic function in a rat model of CHF. In this study we tested the feasibility of upscaling cardiac patch size and surgical deployment in a swine model of CHF to test clinical utility. Methods: Four male Gottingen mini swine 20-25kg and three domestic swine 50-60kg were infarcted using percutaneous methods. Embolizing coils were deployed via catheter distal to the first diagonal branch of the left anterior descending (LAD) coronary artery and animals recovered for 4 weeks. Cardiac patches engineered with bio absorbable polygalactin-910 knitted mesh, dermal fibroblasts and hiPSC-CMs were cultured and implanted on the infarcted epicardium 4 weeks after MI. Cardiac magnetic resonance imaging was performed at baseline, 4 and 8 weeks post MI. All swine were implanted with continuous event recorders to acquire surface electrocardiogram during the entire study. In addition quality of life and functional capacity were assessed through video monitoring and treadmill exertion testing respectively. Infarct size was determined through 2,3,5-triphenyltetrazolium chloride staining. Results: LAD occlusion resulted in a significant (P<0.05) decrease EF (15%), and increase in EDV (59%) and ESV (100%). Average TIMI score decreased from 3.0±0 at time of MI to 1.5±0.6 4wks post MI. Cardiac patches were upsized to 6cm diameter for application in the swine. Patches displayed synchronous and spontaneous contractions within 48hrs. The 6cm patches, when implanted effectively covered the infarcted region bridging viable myocardium. Surgical handling and epicardial deployment was successfully accomplished via median sternotomy. The patches were robust in nature and could be deployed via a minimally invasive robotic procedure. No adverse arrhythmic activity was observed. Implantation of the cardiac patch restored activity levels (quality of life) of patch treated swine vs CHF controls. Conclusion: Our hiPSC-CM cardiac patch can be constructed in a clinical size, easily handled and implanted on the epicardium of the infarcted heart.

Abstract 153: Using the Embryonic Heart as an Instructive Template for Cardiac Tissue Engineering

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Ivan Batalov ◽  
Quentin Jallerat ◽  
Adam W Feinberg
Keyword(s):  
Tissue Engineering ◽  
Heart Muscle ◽  
Cardiac Tissue ◽  
Microcontact Printing ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Tissue Engineering ◽  
Embryonic Heart ◽  
Embryonic Chick ◽  
Tissue Engineering Scaffolds ◽  
Induced Pluripotent

The engineering of highly aligned cardiomyocytes into functional heart muscle remains a primary challenge in cardiac tissue engineering. Researchers have shown that micropatterned topography and chemistry as well as mechanical and electrical gradients are all effective at inducing some degree of alignment. However, which approach works best in terms of electromechanical function of the engineered cardiac muscle is still an active area of research. Because formation of new heart muscle in mammals primarily occurs during cardiogenesis, we asked whether the embryonic heart could be used as an instructive template for the design of more effective cardiac tissue engineering scaffolds. Specifically, we hypothesized that micropatterns of fibronectin based on fibronectin fibril size and architecture in embryonic myocardium could improve cardiomyocyte alignment relative to 20 μm wide, 20 μm spaced fibronectin lines, a control pattern used widely in the literature. To test this, we first imaged the fibronectin matrix in the ventricles of day-5 embryonic chick hearts and imaged this in 3D using a multiphoton microscope. This fibronectin structure was then converted into a photomask for photolithography and subsequent patterning of fibronectin onto cover slips using microcontact printing. Samples with the biomimetic patterns or control patterns were seeded with embryonic chick cardiomyocytes, cultured for 3 days and then stained and imaged to visualize the myofibrils. Image analysis to quantify alignment showed that the ability of the biomimetic pattern to induce cardiomyocyte alignment increased with cell density, suggesting that cell-cell interactions play an important role in the formation of aligned embryonic myocardium. Disruption of the cadherins junctions using blocking antibodies confirmed this conclusion. In the future we will use human induced pluripotent stem cell-derived cardiomyocytes to engineer more clinically-relevant human heart muscle and analyze electromechanical function of the tissues including contractile force and action potential propagation.

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