The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index; 26 of the 64 sources its claims cite were checked for support.
A tissue-engineered scale model of the heart ventricle
Open accessAbstract
Laboratory studies of the heart use cell and tissue cultures to dissect heart function yet rely on animal models to measure pressure and volume dynamics. Here, we report tissue-engineered scale models of the human left ventricle, made of nanofibrous scaffolds that promote native-like anisotropic myocardial tissue genesis and chamber-level contractile function. Incorporating neonatal rat ventricular myocytes or cardiomyocytes derived from human induced pluripotent stem cells, the tissue-engineered ventricles have a diastolic chamber volume of ~500 µl (comparable to that of the native rat ventricle and approximately 1/250 the size of the human ventricle), and ejection fractions and contractile work 50-250 times smaller and 10 4-10 8 times smaller than the corresponding values for rodent and human ventricles, respectively. We also measured tissue coverage and alignment, calcium-transient propagation and pressure-volume loops in the presence or absence of test compounds. Moreover, we describe an instrumented bioreactor with ventricular-assist capabilities, and provide a proof-of-concept disease model of structural arrhythmia. The model ventricles can be evaluated with the same assays used in animal models and in clinical settings.
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33 Own result · 15 Own interpretation · 14 Partly supported · 13 No full text of the sources · 7 No basis given · 4 Supported · 4 Supported so far · 4 Own method · 1 Sources not found · accuracy not yet measured
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In the paper
“ejection fractions and contractile work 50–250 times smaller and 104–108 times smaller than the corresponding values for rodent and human ventricles, respectively.”
- Also stated in: § Discussion · plain
“was less than mouse, rat, or human left ventricles by factors of ~104, 105, and 108, respectively24.”
§ A tissue-engineered scale model of the heart ventricle > Abstract
What the sources say
- Partly supportedcites [24] Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S. & Kass, D. A. Measurement of cardiac function using pressure–volume conductance catheter technique in mice and rats. Nat. Protoc. 3, 1422–1434 (2008). sourceExperimental — accuracy not yet measured
Table 1 (INTRODUCTION; page unavailable) gives stroke-work values for mouse and rat ventricles, providing rodent reference values. It gives no values for engineered or human ventricles and does not establish that engineered ventricles perform 10^4–10^8 times less contractile work. (LLM, conf=0.84)
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- Also stated in: § Discussion · plain
Every source the paper cites for this claim was checked and supports it.
In the paper
“Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have emerged as a promising tool for in vitro cardiology, with the potential to eliminate interspecies and interpersonal variations through patient-specific derivation8.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Supportedcites [8] Karakikes, I., Ameen, M., Termglinchan, V. & Wu, J. C. Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes. Circ. Res. 117, 80–88 (2015). source
The Abstract describes patient-specific iPSC-derived cardiomyocytes as an attractive platform for cardiovascular research and says they could eliminate confounding species-specific and interpersonal variations. This matches the citing sentence’s qualified claim of potential. (LLM, conf=0.95)
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In the paper
“Nanofibers provide biochemical and nano-topographical structural cues with sufficient fidelity to guide cell adhesion, orientation, shape, and assembly40,41.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Supportedcites [40] Capulli, A. K., MacQueen, L. A., Sheehy, S. P. & Parker, K. K. Fibrous scaffolds for building hearts and heart parts. Adv. Drug Deliv. Rev. 96, 83–102 (2016). source
The Abstract says nanofibrous scaffolds can reproduce high-fidelity nanoscale topography and bioactivity, while ECM structure and biochemistry provide cell-instructive cues. The Introduction describes fibrous substrates influencing cell form and arrangement and links scaffold design to cell adhesion and tissue assembly. Together, these support the paraphrase; page numbers are not available in our copy. (LLM, conf=0.88)
- Partly supportedcites [41] Mauck, R. L. et al. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. Tissue Eng. Part B 15, 171–193 (2009). sourceExperimental — accuracy not yet measured
The knee-meniscus case example reports that aligned nanofibrous scaffolds direct cell polarity and promote ordered collagen deposition; “Enhancing cell infiltration” says biologic nanofibers such as collagen provide an environment for cell adhesion. The broader claim that nanofibers generally provide biochemical cues and guide cell shape is not established by these passages; the adhesion point is specifically about biologic fibers. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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In the paper
“These values are comparable to those observed in tissues composed of immature cells where cell geometry, calcium handling, gap junction expression and spatial distribution, as well as other factors limit the conduction velocity when compared to mature tissues52,53.”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
What the sources say
- Partly supportedcites [52] Rohr, S., Kucera, J. P. & Kleber, A. G. Slow conduction in cardiac tissue, I: effects of a reduction of excitability versus a reduction of electrical coupling on microconduction. Circ. Res 83, 781–794 (1998). sourceExperimental — accuracy not yet measured
The Abstract reports conduction velocities in cultured neonatal rat ventricular myocytes and identifies gap-junction coupling and geometry as contributors to slowing. The Minimal Pathlengths Supporting Reentrant Excitation section compares neonatal and adult cell length and gap-junction placement, but does not establish that these features, or calcium handling, make immature tissue conduct more slowly than mature tissue. Its discussion of cell length even predicts slightly higher velocities in cultured cells at a given stage of uncoupling. (LLM, conf=0.86)
- Partly supportedcites [53] Yang, X. L., Pabon, L. & Murry, C. E. Engineering adolescence maturation of human pluripotent stem cell-derived cardiomyocytes. Circ. Res. 114, 511–523 (2014). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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In the paper
“Given that natural contraction rates of cultured cardiomyocytes are ~60–120 bpm (~1–2 Hz)16,49”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Partly supportedcites [16] Mannhardt, I. et al. Human engineered heart tissue: analysis of contractile force. Stem Cell Rep. 7, 29–42 (2016). sourceExperimental — accuracy not yet measured
The Results (Functional Characterization of hiPSC-EHTs; page unavailable) report that engineered heart tissues followed electrical pacing at 1–2 Hz, but that is not their natural contraction rate. In the same section, the reported spontaneous rate before drug treatment was 47 ± 6 bpm, below the claimed ~60–120 bpm range. The paper also studies a specific engineered-tissue model, not cultured cardiomyocytes generally. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [49] Meiry, G. et al. Evolution of action potential propagation and repolarization in cultured neonatal rat ventricular myocytes. J. Cardiovasc. Electrophysiol. 12, 1269–1277 (2001). source
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In the paper
“These features can be recapitulated using nanofibrous materials that are formed into cellular scaffolds with sufficient porosity to support cell infiltration and promote tissue morphogenesis40.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Supportedcites [40] Capulli, A. K., MacQueen, L. A., Sheehy, S. P. & Parker, K. K. Fibrous scaffolds for building hearts and heart parts. Adv. Drug Deliv. Rev. 96, 83–102 (2016). source
The Introduction says fibrous scaffolds can mimic native extracellular matrix and have adequate porosity for cell infiltration and assembly. Section 3 says nanofibers mimic ECM structure and that scaffold porosity is tuned to allow cellular integration and tissue formation, supporting the paraphrase’s point about tissue morphogenesis. Page numbers are not provided in our copy. (LLM, conf=0.92)
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In the paper
“Both NRVM and hiPSC-CM ventricles showed high alignment based on OOP analysis of F-actin stains (Supplementary Fig. 3C), with OOP values of 0. 84 ± 0.02 (NRVM) and 0.85 ± 0.02 (hiPSC-CM).”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
What the sources say
- Partly supportedcites [35] Feinberg, A. W. et al. Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture. Biomaterials 33, 5732–5741 (2012). sourceExperimental — accuracy not yet measured
The Results (§3.3; page unavailable) report OOP-based alignment in engineered tissues made from neonatal rat ventricular myocytes. They do not report hiPSC-CM ventricles or the stated OOP values for either cell type; the paper calculated OOP from α-actinin-stained sarcomere Z-disks rather than F-actin stains. (LLM, conf=0.84)
- Could not verifycites [54] Pasqualini, F. S., Sheehy, S. P., Agarwal, A., Aratyn-Schaus, Y. & Parker, K. K. Structural phenotyping of stem cell-derived cardiomyocytes. Stem Cell Rep. 4, 340–347 (2015). sourceExperimental — accuracy not yet measured
The Orientational Order Parameter section (p. 7) defines OOP as a measure of alignment, but the paper’s Figure 2 discussion (p. 5) analyzes sarcomeric α-actinin in cardiomyocyte tissues, not F-actin staining in NRVM and hiPSC-CM ventricles. Searches for those ventricle measurements and the values 0.84 ± 0.02 and 0.85 ± 0.02 found no matching passage in our copy. (LLM, conf=0.74)
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In the paper
“To begin, we developed a model cardiac chamber based on tabulated structural and functional properties of the human left ventricle40.”
§ A tissue-engineered scale model of the heart ventricle > Model assumptions for tissue-engineered ventricle chambers
What the sources say
- Supportedcites [40] Capulli, A. K., MacQueen, L. A., Sheehy, S. P. & Parker, K. K. Fibrous scaffolds for building hearts and heart parts. Adv. Drug Deliv. Rev. 96, 83–102 (2016). source
The Abstract says the review tabulated structural and functional properties of myocardial tissues for use as design criteria. Section 2.4 also describes tabulated ventricular properties, including left-ventricular elastance. The citing authors attribute the reference properties—not their own development of the model chamber—to this source. (LLM, conf=0.88)
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In the paper
“Healthy ventricular musculature (myocardium) arises from precisely coordinated multiscale integration of physical forces transmitted between cells and the extra-cellular matrix (ECM), as well as between neighboring cells43.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Partly supportedcites [43] Sheehy, S. P., Grosberg, A. & Parker, K. K. The contribution of cellular mechanotransduction to cardiomyocyte form and function. Biomech. Model. Mechanobiol. 11, 1227–1239 (2012). sourceExperimental — accuracy not yet measured
The Introduction describes mechanical forces transmitted between cells and the ECM, and between neighboring cells, as a possible contributor to the form and function of healthy myocardium. It calls multiscale force propagation “one possible mechanism” and says those forces “could prove vital”; the claim presents that proposed role as an established explanation. (LLM, conf=0.86)
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In the paper
“Our observation of isoproterenol-induced stroke work reduction (Fig. 3b) is consistent with negative force-frequency relationships observed in tissues based on immature cardiomyocytes, including NRVM71 and hiPSC-CM72.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [71] Zimmermann, W. H. et al. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol. Bioeng. 68, 106–114 (2000). source
- Supportedcites [72] Germanguz, I. et al. Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells. J. Cell Mol. Med. 15, 38–51 (2011). source
The cited paper’s “Force frequency relations” section reports that increasing stimulation frequency decreased contraction amplitude in both iPS-CM clones, producing statistically significant negative force–frequency relationships. The citing authors’ isoproterenol-induced stroke work reduction is their own observation, not a result attributed to this source. No page number is provided in our copy. (LLM, conf=0.92)
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In the paper
“For example, proliferative hiPSC (line PGP1-iPSC) seeded in our scaffolds at a density of 105 cells/cm2 and cultured according to previously described protocols11 achieved confluence within 4 days of culture (Supplementary Figure S13A, Day 0).”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Partly supportedcites [11] Wang, G. et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat. Med. 20, 616–623 (2014). sourceExperimental — accuracy not yet measured
The Online Methods (labeled Discussion in our copy; page unavailable) describe seeding MACS-purified iPSC-derived cardiomyocytes on muscle thin-film constructs at 10^5 cells/cm², supporting the cited seeding density. They do not describe the PGP1-iPSC line or a protocol for proliferative, undifferentiated hiPSCs. The four-day confluence result is presented as the citing authors’ own observation, not as a finding from this source. (LLM, conf=0.82)
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In the paper
“the positive inotropic effects of isoproterenol observed by others during electrical pacing29 was not observed by us when isoproterenol was administered to spontaneously beating model ventricles (Fig. 3b, right panels).”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Supportedcites [29] Li, R. A. et al. Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells. Biomaterials 163, 116–127 (2018). source
The citation is attached to the positive inotropic effect observed during electrical pacing, not to the citing authors’ finding in spontaneously beating ventricles. In the Results section (‘Pump performance of hvCOC and their responses to pharmacological interventions’), the source reports that isoproterenol significantly increased developed pressure, stroke volume, and stroke work when its model ventricles were paced at 1 Hz. (LLM, conf=0.94)
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In the paper
“ejection fractions and contractile work 50–250 times smaller and 104–108 times smaller than the corresponding values for rodent and human ventricles, respectively.”
- Also stated in: § Discussion · plain
“equivalent to ejection fractions, EF ~ 0.2–1%, which are smaller than expected for healthy mammalian ventricles by factors of roughly 50–250.”
§ A tissue-engineered scale model of the heart ventricle > Abstract
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In the paper
“The two-hole injury generated counter-propagating spiral waves that merged within the region between holes (Fig. 5a, third row).”
§ A tissue-engineered scale model of the heart ventricle > Structural arrhythmia disease model
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In the paper
“Gelatin incorporated into the nanofibers persisted for at least 4 days in aqueous solutions according to measurements made using X-ray photoelectron spectroscopy (Supplementary Fig. S2B).”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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In the paper
“We demonstrated assisted pumping in the absence of drugs by controlling pressure delivered to the external (assist) channel using a pressure-driven programmable pump and cast-molded silicone tricuspid valves to direct flow (Fig. 4a, Supplementary Fig. S9).”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“Synchronous chamber-level contraction was observed for both cell types after 3–5 days of culture in the scaffolds.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
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In the paper
“Here, we used scanning electron microscopy (SEM) to confirm that PCL/gelatin nanofiber scaffolds were structurally comparable with decellularized human left ventricle tissue (Supplementary Fig. S2A).”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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In the paper
“Using parameter values from our scaffolds (R = 5 mm, h = 0.1 mm, 50 kPa < E < 500 kPa) gives bending resonant frequencies of 0.67 Hz < fB < 2 Hz, where fB = ωB/2π, which match the contraction rates of cardiomyocytes.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Not checked — no full text of the sourcecites [50] Morse, P. M. & Feshbach, H. Methods of Theoretical Physics (McGraw-Hill, New York, 1953). source
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In the paper
“Calcium imaging, which has been used as a surrogate for the action potential51, revealed continuous excitation propagation on the ventricle surfaces, confirming electrical continuity throughout the ventricle constructs (Fig. 1d, Supplementary Movies 6,7).”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
What the sources say
- Not checked — no full text of the sourcecites [51] Mandegar, M. A. et al. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell 18, 541–553 (2016). source
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In the paper
“Immunostaining confirmed fiber-directed anisotropic cell alignment and infiltration within the chamber wall (Fig. 2, Supplementary Fig. S3, S4, Supplementary Movie 8)”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
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In the paper
“Furthermore, we observed an expected reduction in beat rate, as judged by a shift in the frequency spectrum, as bath temperature was decreased from physiological 37°C to less than ~30°C (Supplementary Fig. S7C).”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
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In the paper
“The tensile elastic modulus of our scaffolds was anisotropic, with values measured longitudinally (in the direction parallel to the fiber axis), EL = 500 ± 31 kPa, or transverse (in the direction perpendicular to the fiber axis), ET = 74 ± 15 kPa (Supplementary Fig. S2C).”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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In the paper
“we monitored ventricle contraction by ultrasound through removable elastomeric windows in the HBR (Fig. 4c, Supplementary Fig. S10, Supplementary Movies 10,11).”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“Preliminary work in our laboratories suggest that we can achieve extended culture periods for NRVM (Supplementary Fig. S12, Supplementary Movies S14, 15) and hiPSC-CM (Supplementary Figs. S13, S14) in our nanofibrous scaffolds.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“Calcium mapping of pre-injured ventricles was done on day 11 but tissue had grown into the injury site, preventing stable rotor pinning.”
§ A tissue-engineered scale model of the heart ventricle > Methods > Optical mapping experiments
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In the paper
“Volume estimated by calculating the slope of measured conductance versus cuvette volume (Supplementary Fig. 4B.i) or by scaffold filling (Supplementary Fig. 4B.ii) were in good agreement within a relevant working volume range of ~300–600 μL.”
§ A tissue-engineered scale model of the heart ventricle > Methods > Pressure-Volume Measurements
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In the paper
“Precise anatomical defects applied to our tissue engineered model ventricles generated stable pinned rotors and spiral waves (Fig. 5, Supplementary Fig. 11, Supplementary Movies S12, S13)”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“contractile strength increased in our preliminary extended culture period experiments (Supplementary Fig. S14).”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“The model ventricles can be evaluated with the same assays used in animal models and in clinical settings.”
§ A tissue-engineered scale model of the heart ventricle > Abstract
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In the paper
“and suggest that model ventricles are suitable for cardiac arrhythmia studies.”
- Also stated in: § Structural arrhythmia disease model · hedged
“These results suggest the feasibility of using tissue engineered heart chambers to study arrhythmogenic heart diseases.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
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- Also stated in: § Structural arrhythmia disease model · hedged
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, the lack of in vitro models based on hiPSC-CM that accurately reproduce the architecture and functional output of the heart chambers9,10,23 is a significant limitation because tissue performance cannot be directly compared to animal or human heart performance, which are evaluated by measuring changes in chamber pressure and volume24,25.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Not checked — no full text of the sourcecites [9] Feric, N. T. & Radisic, M. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Adv. Drug Deliv. Rev. 96, 110–134 (2016). source
- Not checked — no full text of the sourcecites [10] Eder, A., Vollert, I., Hansen, A. & Eschenhagen, T. Human engineered heart tissue as a model system for drug testing. Adv. Drug Deliv. Rev. 96, 214–224 (2016). source
- Not checked — no full text of the sourcecites [23] Mathur, A., Ma, Z., Loskill, P., Jeeawoody, S. & Healy, K. E. In vitro cardiac tissue models: current status and future prospects. Adv. Drug Deliv. Rev. 96, 203–213 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Our findings confirm that tissue-engineered model ventricle contraction can be monitored by catheter sensors”
§ A tissue-engineered scale model of the heart ventricle > Introduction
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In the paper
“This suggests a natural design principal to engineer artificial ventricles as a function of the natural frequencies of cardiomyocyte contraction.”
- Also stated in: § Discussion · hedged
“Our calculations of resonant bending frequencies suggests a natural design principal to engineer cardiac chambers as a function of their intended beat rates.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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- Also stated in: § Discussion · hedged
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In the paper
“PCL provides structural stability for the scaffold’s nanofibrous features during culture”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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In the paper
“In myocardial tissues, anatomical structures can introduce heterogeneities of impulse conduction that lead to ventricular tachycardia, including spiral waves anchored to anatomical defects33,62.”
§ A tissue-engineered scale model of the heart ventricle > Structural arrhythmia disease model
What the sources say
- Not checked — no full text of the sourcecites [33] Kleber, A. G. & Rudy, Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol. Rev. 84, 431–488 (2004). source
- Not checked — no full text of the sourcecites [62] Lim, Z. Y., Maskara, B., Aguel, F., Emokpae, R.Jr & Tung, L. Spiral wave attachment to millimeter-sized obstacles. Circulation 114, 2113–2121 (2006). source
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In the paper
“Overnight exposure to UV was sufficient to prevent bacterial contamination”
§ A tissue-engineered scale model of the heart ventricle > Methods > Scaffold fabrication
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In the paper
“the capability to tissue-engineer functional model ventricles, and the modular bioreactor technologies designed for in situ instrumentation and functional assessment, provide a suitable system for in vitro cardiology studies that increasingly translate to clinical outcomes.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“our results demonstrate the feasibility of engineering functional scale models of the heart chambers, where tissue assembly is guided by a nanofibrous culture substrate”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“our structural arrhythmia disease model reaffirmed the importance of building native-like anisotropic tissues”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“the importance of building native-like anisotropic tissues that are important for both normal propagation and arrhythmogenesis33.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [33] Kleber, A. G. & Rudy, Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol. Rev. 84, 431–488 (2004). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“our design rules provide a path toward engineering heart chambers with functional performance increasingly comparable to native organs.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“we verified that pressure and volume variations generated by our tissue engineered model ventricles were above the noise floor (Supplementary Figs. S5–S7).”
§ A tissue-engineered scale model of the heart ventricle > Methods > Pressure-Volume Measurements
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In the paper
“A direct comparison of engineered ventricle chamber contractile performance with those of ex-vivo animal studies is challenging.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 11
- It may state two separate claims as one. 43
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In the paper
“animal models and isolated heart preparations are evaluated using pre-clinical and clinical measurement modalities such as catheterization3, echocardiography4, and magnetic resonance imaging5.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Partly supportedcites [3] Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S. & Kass, D. A. Measurement of cardiac function using pressure–volume conductance catheter technique in mice and rats. Nat. Protoc. 3, 1422–1434 (2008). sourceExperimental — accuracy not yet measured
The Introduction describes catheterization to measure cardiac function in mouse and rat animal models, including intact beating hearts. It does not establish the cited technique's use in isolated heart preparations. Citation 3 is attached to catheterization, so the separate echocardiography and MRI citations are not assessed here. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [4] Ram, R., Mickelsen, D. M., Theodoropoulos, C. & Blaxall, B. C. New approaches in small animal echocardiography: imaging the sounds of silence. Am. J. Physiol. Heart Circ. Physiol. 301, H1765–1780 (2011). source
- Not checked — no full text of the sourcecites [5] Bakermans, A. J. et al. Small animal cardiovascular MR imaging and spectroscopy. Prog. Nucl. Magn. Reson. Spectrosc. 88–89, 1–47 (2015). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
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In the paper
“Data obtained using these methods allow direct comparison to patient data, but differences in genetics, physiology and disease etiology limit the utility of animal models for developing therapeutic interventions6,7.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Not checked — no full text of the sourcecites [6] Chandrasekera, P. C. & Pippin, J. J. The human subject: an integrative animal model for 21st century heart failure research. Am. J. Transl. Res. 7, 1636–1647 (2015).
- Partly supportedcites [7] Gloschat, C. R. et al. Arrhythmogenic and metabolic remodelling of failing human heart. J. Physiol. 594, 3963–3980 (2016). sourceExperimental — accuracy not yet measured
The Introduction says animal models may not reproduce the varied causes of human heart failure and that these differences limit translation to clinical therapies. The Conclusions also identify species and physiological differences as barriers. Our copy does not establish that data obtained using the citing paper’s methods allow direct comparison with patient data, or specifically identify genetic differences between animal models and humans as a barrier. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The myocardial ECM is fibrillar, anisotropic, and provides nanotopographical cues that guide cardiomyocyte alignment and assembly44, ultimately forming a helicoid structure that optimizes ejection fraction during ventricular contraction45.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Supportedcites [44] Kim, D. H. et al. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc. Natl Acad. Sci. USA 107, 565–570 (2010). source
Citation 44 is attached to the claim about myocardial ECM and cardiomyocyte alignment and assembly, not the subsequent helicoid and ejection-fraction claim attributed to citation 45. The Results describe aligned ECM fibrils whose orientation correlates with adjacent myocardial cells and suggest that the ECM provides nanotopographic cues guiding alignment; they also report that nanoscale patterns guide cell monolayers into an aligned architecture. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [45] Savadjiev, P. et al. Heart wall myofibers are arranged in minimal surfaces to optimize organ function. Proc. Natl Acad. Sci. USA 109, 9248–9253 (2012). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
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In the paper
“Engineered cardiac organoid chambers comprised of cardiomyocytes embedded in isotropic hydrogels showed significant promise for obtaining intra-ventricular pressure measurements26–29 but the lack of a scaffold to guide cell assembly hampers the formation of organized tissues that recapitulate the laminar architecture30,31 of the native myocardium.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Not checked — no full text of the sourcecites [26] Lee, E. J., Kim do, E., Azeloglu, E. U. & Costa, K. D. Engineered cardiac organoid chambers: toward a functional biological model ventricle. Tissue Eng. Part A 14, 215–225 (2008). source
- Not checked — no full text of the sourcecites [27] Gonen-Wadmany, M., Gepstein, L. & Seliktar, D. Controlling the cellular organization of tissue-engineered cardiac constructs. Ann. N. Y. Acad. Sci. 1015, 299–311 (2004). source
- Not checked — no full text of the sourcecites [28] Yildirim, Y. et al. Development of a biological ventricular assist device: preliminary data from a small animal model. Circulation 116, I-16–I-23 (2007). source
- Partly supportedcites [29] Li, R. A. et al. Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells. Biomaterials 163, 116–127 (2018). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [30] Costa, K. D., Takayama, Y., McCulloch, A. D. & Covell, J. W. Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium. Am. J. Physiol. 276, H595–607 (1999). source
- Not checked — no full text of the sourcecites [31] Arts, T., Costa, K. D., Covell, J. W. & McCulloch, A. D. Relating myocardial laminar architecture to shear strain and muscle fiber orientation. Am. J. Physiol. Heart Circ. Physiol. 280, H2222–2229 (2001). source
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We selected polycaprolactone (PCL)/gelatin nanofibers as our material of choice because they are biocompatible and biodegradable, they promote cell adhesion, provide sufficient structural integrity for ventricle culture and catheterization, and can be produced by a variety of nanofiber production systems that include electrospinning and force-spinning methods40.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Partly supportedcites [40] Capulli, A. K., MacQueen, L. A., Sheehy, S. P. & Parker, K. K. Fibrous scaffolds for building hearts and heart parts. Adv. Drug Deliv. Rev. 96, 83–102 (2016). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the native heart, overlapping myocardial fibers are arranged into distinct laminae four to six myocytes thick and separated from adjacent laminae by an extracellular collagen network42.”
§ A tissue-engineered scale model of the heart ventricle > Model assumptions for tissue-engineered ventricle chambers
What the sources say
- Partly supportedcites [42] Pope, A. J., Sands, G. B., Smaill, B. H. & LeGrice, I. J. Three-dimensional transmural organization of perimysial collagen in the heart. Am. J. Physiol. Heart C 295, 1243–1252 (2008). sourceExperimental — accuracy not yet measured
The Discussion (3-D perimysial collagen organization; page unavailable) describes branching myocardial layers grouped by perimysial collagen and reports them as approximately four cells thick, not four to six. The Results (page unavailable) show collagen between adjacent layers, but the paper also says laminar structure is not evident in the outer 10–20% of the rat left ventricle, so the claim is too general. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Cardiomyocyte spontaneous beat rates in our model ventricles were similar to other in vitro assays based on NRVM49 or hiPSC-CM16, showing moderate positive chronotropy (~40% beat rate)10,18.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [49] Meiry, G. et al. Evolution of action potential propagation and repolarization in cultured neonatal rat ventricular myocytes. J. Cardiovasc. Electrophysiol. 12, 1269–1277 (2001). source
- Supportedcites [16] Mannhardt, I. et al. Human engineered heart tissue: analysis of contractile force. Stem Cell Rep. 7, 29–42 (2016). source
The citation to this paper is attached to the hiPSC-CM assay, not the later ~40% positive-chronotropy claim, which has separate citations. The Results (Functional Characterization of hiPSC-EHTs) describe spontaneously beating hiPSC-derived heart tissues and report a baseline rate of 47 ± 6 bpm, supporting its use as an example of that assay. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [10] Eder, A., Vollert, I., Hansen, A. & Eschenhagen, T. Human engineered heart tissue as a model system for drug testing. Adv. Drug Deliv. Rev. 96, 214–224 (2016). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The moderate positive chronotropy and reduction of stroke work observed at high isoproterenol doses are characteristic of immature tissues exhibiting poorly developed calcium handling properties8, suggesting that maturation protocols14,21,22,73 may be required to obtain positive force-frequency relationships, as observed in healthy adult human ventricular myocardium74.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Partly supportedcites [8] Karakikes, I., Ameen, M., Termglinchan, V. & Wu, J. C. Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes. Circ. Res. 117, 80–88 (2015). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [14] Nunes, S. S. et al. Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat. Methods 10, 781–787 (2013). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [74] Endoh, M. Force–frequency relationship in intact mammalian ventricular myocardium: physiological and pathophysiological relevance. Eur. J. Pharmacol. 500, 73–86 (2004). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Contractile work in our ventricle models was measured using conductance catheters and was smaller than reported for cardiac organoid chambers based on NRVM26 or pluripotent hES2 human embryonic stem cell-derived cardiomyocytes29, where volume changes were indirectly assessed from video recordings.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [26] Lee, E. J., Kim do, E., Azeloglu, E. U. & Costa, K. D. Engineered cardiac organoid chambers: toward a functional biological model ventricle. Tissue Eng. Part A 14, 215–225 (2008). source
- Supportedcites [29] Li, R. A. et al. Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells. Biomaterials 163, 116–127 (2018). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, the tensile elastic modulus of our scaffold in the direction of fiber alignment (EL ~ 500 kPa) was higher than healthy ventricular ECM (E ~350 kPa)68 and may have limited cardiomyocyte shortening during contraction.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Partly supportedcites [68] Quinn, K. P. et al. Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction. Sci. Rep. 6, 35823 (2016). sourceExperimental — accuracy not yet measured
The Results report tensile testing of healthy ventricular ECM and its elastic modulus, supporting the use of this paper as a comparator. But the available text does not give the cited value of approximately 350 kPa (searched: “350” and “kPa”). The scaffold modulus and possible effect on cardiomyocyte shortening are the citing authors’ own comparison and inference, not findings attributed to this source. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Incorporating neonatal rat ventricular myocytes or cardiomyocytes derived from human induced pluripotent stem cells, the tissue-engineered ventricles have a diastolic chamber volume of ~500 μL (comparable to that of the native rat ventricle and approximately 1/250 the size of the human ventricle)”
§ A tissue-engineered scale model of the heart ventricle > Abstract
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we report tissue-engineered scale models of the human left ventricle, made of nanofibrous scaffolds that promote native-like anisotropic myocardial tissue genesis and chamber-level contractile function.”
§ A tissue-engineered scale model of the heart ventricle > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In all cases, spontaneous calcium activity showed stable excitation patterns with plane waves (healthy) or pinned spiral waves (injured) repeating at a near-constant rate (between 4 Hz and 5Hz) for the duration of experiments (~2 hours).”
§ A tissue-engineered scale model of the heart ventricle > Structural arrhythmia disease model
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pressure/volume loops measured before and after isoproterenol exposure showed an isoproterenol-induced reduction in stroke work, concomitant with an increase in beat frequency (Fig. 3b,c).”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plane wave propagation was observed prior to injury (Fig. 5a, top), whereas injured ventricles generated spiral waves that were pinned to the controlled anatomical defects (Fig. 5a, bottom panels, and Supplementary Movie 12).”
§ A tissue-engineered scale model of the heart ventricle > Structural arrhythmia disease model
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The HBR includes both intra- and extra- ventricular flow loops, separate chambers for optional valve inserts, and additional access ports for catheters (Fig. 4a, Supplementary Fig. S8).”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean calcium wavefront propagation velocity from apex to base was 9.33 cm/sec or 5.2 cm/sec for NRVM or hiPSC-CM ventricles, respectively.”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The resulting tissue-engineered ventricle chambers were sutured to tubing or bioreactor components through which catheter sensors were introduced and stable contraction of both NRVM and hiPSC-CM ventricles permitted time-dependent pressure and volume measurements.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“In our scaffold, gelatin was used to enhance cell and biomolecule adhesion during cell seeding, and the polymer backbone (PCL) provided structural features (microporosity, nanotopography, anisotropy) that resisted degradation during culture.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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“Calcium fluorescence intensity measured near the rotor poles of a single-hole injury model showed consistent phase difference and a rotation rate of ~ 5 Hz (Fig. 5b, Supplementary Figure S12, and Supplementary Movie 13).”
§ A tissue-engineered scale model of the heart ventricle > Structural arrhythmia disease model
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“Using small animal echocardiography equipment, we recorded both unassisted natural spontaneous ventricle contraction (Fig. 4c, left, and Supplementary Movie 10) and HBR-assisted contraction (Fig. 4c, right, and Supplementary Movie 11).”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“Measured differences in chamber pressure were ~50 μmHg (rat or human) and the volume change was ~5 μL (rat) or 1 μL (human).”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
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In the paper
“Synchronous, coordinated ventricle contraction developed spontaneously after 3–5 days of culture (Supplementary Movies 3,4) and persisted for the duration of experimental procedures (Supplementary Movie 5), conducted 14 days after seeding.”
§ A tissue-engineered scale model of the heart ventricle > Tissue-engineered ventricle chamber
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In the paper
“Cyclic pressure applied to the extra-ventricular loop drives intra-ventricular fluid flow via assisted ventricle contraction, and unidirectional flow can be achieved using commercially available valves or with custom valve inserts in the HBR.”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“Ventricle beat rates showed a positive chronotropic response over the concentration range in both the NRVM and hiPSC-CM ventricles (Fig. 3c), as expected for healthy NRVM59, hiPSC-CM60, engineered hiPSC-CM cardiac tissues16, and human patients61.”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
What the sources say
- Not checked — no full text of the sourcecites [59] Simpson, P. & Savion, S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol. Circ. Res. 50, 101–116 (1982). source
- Not checked — no full text of the sourcecites [60] Moretti, A. et al. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N. Engl. J. Med. 363, 1397–1409 (2010). source
- Not checked — no full text of the sourcecites [61] Koglin, J., Bohm, M., Vonscheidt, W., Stablein, A. & Erdmann, E. Antiadrenergic effect of carbachol but not of adenosine on contractility in the intact human ventricle in-vivo. J. Am. Coll. Cardiol. 23, 678–683 (1994). source
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In the paper
“The spontaneous beat rate of NRVM ventricles (~130 ±15 bpm) was higher than hiPSC-CM ventricles (~85 ± 15 bpm), and both increased by ~40% following exposure to 10−4 M isoproterenol.”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
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In the paper
“These features provided sufficient structural integrity for ventricle culture and they guided cardiomyocyte assembly”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“Thus, ejection fractions were ~1% (rat) or ~0.2% (human) and stroke work was WS ~ 0.25 mmHg × μL (rat) or WS ~ 0.05 mmHg × μL (human).”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
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In the paper
“Whereas regular beat frequencies were observed in calcium-containing M199 or Tyrode’s solution, exposure to calcium-free PBS led to broad beat rate distributions (Supplementary Fig. S7B).”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
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In the paper
“We also cultured a non-proliferative hiPSC-CM line (Cor.4U) in model ventricle scaffolds for 6 months, demonstrating that tissue anisotropy was preserved (Supplementary Figure S14A) and stable pressure-volume loops could be recorded (Supplementary Figure S14 B).”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“When cultured in differentiation media, the resulting hiPSC-CM showed spontaneous contraction and early stages of sarcomeric assembly within 8–12 days of culture (Supplementary Figure S13A, Day 12), and anisotropic sarcomeric assembly with early stages of z-disk alignment after 1 month in culture (Supplementary Figure S13A, Day 30).”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“Both types of model cardiac chambers generated similarly shaped elliptical PV-loops (Fig. 3b, Supplementary Fig. S14), which are expected from ventricles contracting in the absence of valves and show similarities to PV loops obtained from patients with severe valvular insufficiencies78.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not matchedcites [78] Klabunde, R. E. Cardiovascular Physiology Concepts 2nd edn (Lippincott Williams & Wilkins/Wolters Kluwer, Philadelphia, 2012).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The EF of our tissue-engineered rat ventricles was ~1% (1/50 EF of healthy rats), suggesting that discontinuities in cardiomyocyte coverage limited tissue-engineered ventricle contractile strength.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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In the paper
“We observed a non-linear conductance/volume catheter response (Supplementary Fig. 4B.i), as expected for these systems82.”
§ A tissue-engineered scale model of the heart ventricle > Methods > Pressure-Volume Measurements
What the sources say
- Not checked — no full text of the sourcecites [82] Pearce, J. A., Porterfield, J. E., Larson, E. R., Valvano, J. W. & Feldman, M. D. Accuracy considerations in catheter based estimation of left ventricular volume. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2010, 3556–3558 (2010). source
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In the paper
“Both showed evidence of spontaneously generated calcium plane wave propagation but one had greater homogeneity; this favorable sample is reported in our revised manuscript.”
§ A tissue-engineered scale model of the heart ventricle > Methods > Optical mapping experiments
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In the paper
“The cell density in our ventricles, estimated by counting immunostained (DAPI) NRVM ventricle surfaces and cross-sections (Supplementary Fig. S3), was ~90,000 cells/mm3 for a total cell number ~2.3 × 106 in a 26 mm3 scaffold volume, which is approximately 10-fold less than in 21-day-old or 3-month-old rat hearts75.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [75] Bai, S. L., Campbell, S. E., Moore, J. A., Morales, M. C. & Gerdes, A. M. Influence of age, growth, and sex on cardiac myocyte size and number in rats. Anat. Rec. 226, 207–212 (1990). source
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In the paper
“but direct comparison with natural ventricle pressure and volume dynamics requires three-dimensional (3D) contractile cardiac chambers.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
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In the paper
“These cells are assembled into functional engineered heart tissues2,9,10, including muscular thin films11,12 or 3D muscle strips13–20, to model contractile pathophysiologies11, promote hiPSC-CM maturation9,14,15,21, and produce drug responses that are increasingly comparable to human patients16,18,22.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
What the sources say
- Not checked — no full text of the sourcecites [2] Tzatzalos, E., Abilez, O. J., Shukla, P. & Wu, J. C. Engineered heart tissues and induced pluripotent stem cells: macro- and microstructures for disease modeling, drug screening, and translational studies. Adv. Drug Deliv. Rev. 96, 234–244 (2016). source
- Not checked — no full text of the sourcecites [9] Feric, N. T. & Radisic, M. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Adv. Drug Deliv. Rev. 96, 110–134 (2016). source
- Not checked — no full text of the sourcecites [10] Eder, A., Vollert, I., Hansen, A. & Eschenhagen, T. Human engineered heart tissue as a model system for drug testing. Adv. Drug Deliv. Rev. 96, 214–224 (2016). source
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In the paper
“These and other limitations associated with animal models, for example high maintenance costs and low experimental throughput, motivate the development of alternative in vitro cardiology assays based on human cells.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
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In the paper
“These properties allowed us to fabricate ventricle scaffolds that were both structurally stable and permissive to chamber contraction by cardiomyocyte shortening.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
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In the paper
“Echocardiography performed in the absence of extra-ventricular tissues can improve image clarity compared with in vivo studies, underscoring the advantage of organ modularity in our HBR.”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“In this configuration, cultured ventricles can be exposed to externally-controlled physiological or pathological pressure variations and PV loops acquired with or without valves (Fig. 4b)”
§ A tissue-engineered scale model of the heart ventricle > Bioreactor for modular assembly of ventricles and valves
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In the paper
“We previously described anisotropic PCL/gelatin nanofiber production by pull spinning and their use to guide skeletal muscle tissue assembly46.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Not checked — no full text of the sourcecites [46] Deravi, L. F. et al. Design and fabrication of fibrous nanomaterials using pull spinning. Macromol. Mater. Eng. 302, 1600404 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Scaffold engineering should account for the fact that the myocardium is a composite in which the dominant stiffness shifts from myocytes to the ECM with increasing strain67, emphasizing the ECM’s role maintaining structural integrity.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
What the sources say
- Not checked — no full text of the sourcecites [67] Chaturvedi, R. R. et al. Passive stiffness of myocardium from congenital heart disease and implications for diastole. Circulation 121, 979–988 (2010). source
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In the paper
“These results have implications for preclinical cardiology and regenerative medicine research where human organ models are sought to improve translation of therapeutic strategies.”
§ A tissue-engineered scale model of the heart ventricle > Introduction
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“A fundamental aspect of myocardial function is the response to adrenergic agonists, which has been studied extensively in both rodents and humans, making β-adrenergic response a good test of the ability of our engineered ventricles to recapitulate normal cardiac pharmacology57,58.”
§ A tissue-engineered scale model of the heart ventricle > Intra-ventricular pressure and volume measurements
What the sources say
- Not checked — no full text of the sourcecites [57] Barrett, A. M. & Carter, J. Comparative chronotropic activity of beta-adrenoceptive antagonists. Br. J. Pharmacol. 40, 373–381 (1970). source
- Not checked — no full text of the sourcecites [58] Brito-Martins, M., Harding, S. E. & Ali, N. N. Beta(1)- and beta(2)-adrenoceptor responses in cardiomyocytes derived from human embryonic stem cells: comparison with failing and non-failing adult human heart. Br. J. Pharmacol. 153, 751–759 (2008). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“while gelatin was chosen as an RGD-containing biopolymer derived from denatured collagen that improves scaffold binding to cells and biomolecules such as fibronectin47,48.”
§ A tissue-engineered scale model of the heart ventricle > Ventricle scaffold
What the sources say
- Not checked — no full text of the sourcecites [47] Ruoslahti, E. RGD and other recognition sequences for integrins. Annu Rev. Cell Dev. Biol. 12, 697–715 (1996). source
- Not checked — no full text of the sourcecites [48] Katagiri, Y., Brew, S. A. & Ingham, K. C. All six modules of the gelatin-binding domain of fibronectin are required for full affinity. J. Biol. Chem. 278, 11897–11902 (2003). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These preliminary results suggest that our scaffolds support functional myocardial tissue production using relatively small numbers of seeded hiPSC that can subsequently be cultured for extended time periods.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Our use of conductance catheters was advantageous for direct volume readouts but electrical pacing during catheterization was not recommended by the catheter manufacturer and therefore not performed in these studies.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All procedures were approved by the Harvard Animal Care and Use Committee”
§ A tissue-engineered scale model of the heart ventricle > Methods > Experimental animals
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In the paper
“Our work suggests that including a nanofibrous component to printable inks would be advantageous for directing cardiomyocyte shape and assembly in printed scaffolds or tissues.”
§ A tissue-engineered scale model of the heart ventricle > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
The scale-model ventricle would have a diastolic chamber volume of about 500 microliters, about twice that of a rat and about 1/250 that of a human.
“We would build a scale-model of the human left ventricle chamber with diastolic chamber volume ~500 microliters (~2 × rat, ~1/250 human)”
The authors state this as an assumption.
The ventricle wall would not be vascularized and its thickness would be limited to about 0.1 mm to maintain high cell viability in a diffusion-limited environment.
“the ventricle wall would not be vascularized and its thickness limited to ~0.1 mm (~1/10 rat, ~1/100 human) to maintain high cell viability within the diffusion-limited environment”
The authors state this as an assumption.
The ventricle scaffold material would be a well-known protein-polymer mixture to ensure production reproducibility using existing nanofiber systems.
“the ventricle scaffold material would be a well-known protein-polymer mixture to ensure production reproducibility using existing nanofiber systems”
The authors state this as an assumption.
Cardiomyocyte alignment would be circumferential throughout the scaffold, representing a thin-walled approximation of the helical alignment within the native ventricular wall.
“cardiomyocyte alignment would be circumferential throughout the scaffold, representing a thin walled approximation of the helical alignment within the native ventricular wall.”
The paper relies on this without support.
The rat is the current industry standard for studying heart disease in vitro and in vivo.
“rat is the current industry standard for the study of heart disease in vitro and in vivo”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“However, they only cultivated pure cardiomyocytes within 14 days after seeding.”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [20]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We calculated our hiPSC-CM based ventricular volumetric change between peak contraction and peak relaxation to be 5.94 ± 1.66 % (n = 4, mean ± SEM, Fig. 4g), which is 2~5 and 8~20 times higher than values previously reported (ejection fraction) for NRVM and hiPSC-CM in vitro ventricle models, respectively13, 15, 32.”
From Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles (2023) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, these tissues are limited to a single ventricle model and thus lack the capacity for perfusion.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Wall thicknesses on the low end of this spectrum match what has been previously demonstrated in the literature, and the high end of the spectrum far exceeds existing tissue models6–8.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Engineered cardiac chambers have emerged to address this gap, enabling physiologically relevant pressure-volume measurements and capturing both contractile and diastolic dynamics that mimic aspects of native cardiac hemodynamics.”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, Michas et al. and Macqueen et al. successfully incorporated valves into microfluidic and bioreactor platforms, respectively, with Michas et al. demonstrating unidirectional flow and MacQueen et al. reporting improved PV loop morphology as a result of valve presence (Michas et al., 2022; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An additional disease model, a structural arrhythmia model induced by cryoinjury, was described by MacQueen et al. (2018). This approach produced pinned spiral wave patterns that are consistent with clinical arrhythmia phenotypes.”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These models more closely resemble the structural architecture of the heart, pump fluid, allow for analysis of Pressure-Volume (PV) readouts, facilitate control of preload and afterload, and are exposed to multiaxial stress (Li et al., 2018; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, Michas et al. and Macqueen et al. successfully incorporated valves into microfluidic and bioreactor platforms, respectively, with Michas et al. demonstrating unidirectional flow and MacQueen et al. reporting improved PV loop morphology as a result of valve presence (Michas et al., 2022; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These models more closely resemble the structural architecture of the heart, pump fluid, allow for analysis of Pressure-Volume (PV) readouts, facilitate control of preload and afterload, and are exposed to multiaxial stress (Li et al., 2018; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Anatomically, select models have incorporated functional valves, producing more physiological PV loops (MacQueen et al., 2018; Michas et al., 2022).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Simultaneous PV measurements are currently limited to invasive micro-catheter systems adapted from in vivo mouse experiments (Li et al., 2018; MacQueen et al., 2018; Kupfer et al., 2020; Mohammadi et al., 2022).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“While this scaffold-based approach facilitated enhanced CM orientation, the rigidity and non-degradable nature of the scaffolds hampered cellular self-organization and matrix self-determination, preventing the cells from forming a cohesive tissue and impairing the full potential contractility of the cardiomyocytes.”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, valve-less engineered cardiac chambers exhibit less distinct delays between pressure and volume fluctuations during beating cycles, typically leading to narrower, elliptical PV-loop patterns (R. A. Li et al., 2018;Macqueen et al., 2018).”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“While there are a few models that can effectively mimic the pumping function of the heart, they are typically associated with significant cost and labor intensity.[ 19 , 20 ]”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Starting with the frequency changes, we can confirm data showing an increase of around 88% after 10 µM ISO treatment reported by Hamad et al.[ 17 ] and around 15 % reported by MacQueen et al.,[ 20 ] with measurements showing an increase of 30.6 to 45.9%.”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The mean beating frequency in their model was about 85 bpm,[ 20 ] which is comparable to our engineered ventricles.”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“MacQueen et al. generated a ventricle model by seeding human cardiomyocytes onto an electrospun ventricle scaffold and measured a volume change during a contraction cycle of approximately 0.4 µL.[ 20 ]”
From Engineered in vitro multi-cell type ventricle model generates long-term pulsatile flow and modulates cardiac output in response to cardioactive drugs (2025) · cites this paper as [20]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Because fiber-spinning techniques can reproduce these fine spatial features with higher throughputs, they offer a potential solution and have been used previously to engineer tissue scaffolds, such as heart valves (23) and ventricle models (24).”
From Recreating the heart's helical structure-function relationship with focused rotary jet spinning (2022) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“These values were consistent with previous reports of in vitro tissues composed of immature cardiomyocytes, where factors such as geometry, calcium handling, and gap junction expression can influence CV (24, 34, 35).”
From Recreating the heart's helical structure-function relationship with focused rotary jet spinning (2022) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“Although the metrics presented here (e.g., EF) were greater (by a factor of ~3) than for recently reported in vitro ventricle models (24, 39), they were still substantially lower than in vivo values (tables S2 and S3).”
From Recreating the heart's helical structure-function relationship with focused rotary jet spinning (2022) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, multiple existing single ventricle models rely on their simple cup-like geometry to enable casting of a cardiomyocyte-laden gel6 or seeding of cardiomyocytes after fabrication7.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“To address this issue, researchers have made strides in the generation of volume-handling cardiac tissue models capable of recapitulating pressure-volume dynamics of the heart6–8.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“These measurements are on par with data shown in single ventricle models6, 7.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, we show that the hChaMP can maintain these functions for at least 6 weeks, while most similar models have been characterized only up to 2 weeks after fabrication6–8, 18.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“similar to results reported by MacQueen et al., we show that the hChaMP can respond to a range of isoproterenol doses7.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“the pressure generated by the hChaMP, while low (0.23 mmHg), is higher than other reported values6, 7.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“These models more closely resemble the structural architecture of the heart, pump fluid, allow for analysis of Pressure-Volume (PV) readouts, facilitate control of preload and afterload, and are exposed to multiaxial stress (Li et al., 2018; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“These models more closely resemble the structural architecture of the heart, pump fluid, allow for analysis of Pressure-Volume (PV) readouts, facilitate control of preload and afterload, and are exposed to multiaxial stress (Li et al., 2018; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“Incorporation of valves is critical for reproducing physiologic PV loops and ensuring unidirectional flow (MacQueen et al., 2018; Michas et al., 2022).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“These models more closely resemble the structural architecture of the heart, pump fluid, allow for analysis of Pressure-Volume (PV) readouts, facilitate control of preload and afterload, and are exposed to multiaxial stress (Li et al., 2018; MacQueen et al., 2018).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as MacQueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“However, current fabrication approaches used to create these engineered ventricular chambers, including molding (R. A. Li et al., 2018), scaffold-seeding (Macqueen et al., 2018;Michas et al., 2022;Mohammadi et al., 2022;Patel & Birla, 2018) and bioprinting (Kupfer et al., 2020;Lee et al., n.d.) have significant limitations that hamper their use.”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, functional characterization of current engineered ventricles is often done utilizing conductance catheters (Kupfer et al., 2020;R. A. Li et al., 2018;Macqueen et al., 2018), which come with high costs, low accessibility and incompatibility with electrical pacing (Baan et al., 1985;Wei et al., 2014).”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“Although far from human ejection fraction values (50%-70%), the ejection fractions of our mini-heart (~1%-3%) are in the same range as other reported models (0.2%-9.6%) (Kupfer et al., 2020;R. A. Li et al., 2018;Macqueen et al., 2018;Michas et al., 2022).”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“However, the observed negative force-frequency relationship is consistent with findings in similar models (R. A. Li et al., 2018;Macqueen et al., 2018) and suggests the calcium handling of hPSC-CMs still requires further maturation.”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“The mini-hearts demonstrated stroke works of ~0.10 -~0.18 µJ which, to our knowledge, are the highest stroke work values compared to other engineered ventricles (6 nJ-57 nJ) (Kupfer et al., 2020;R. A. Li et al., 2018;Macqueen et al., 2018).”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Macqueen et al., 2018
In the citing paper
“Recent examples have also demonstrated that the introduction of electrical barriers such as holes in healthy cardiac tissue or fibroblast dense regions disrupts action potential propagation46,52.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [52]
Citations
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“…(hPSC) have focused on generating ventricular myocardium (Ahn et al., 2018; Eschenhagen et al., 2012; Lemoine et al., 2017; Lind et al., 2017a; MacQueen et al., 2018; Nunes et al., 2013; Schaaf et al., 2011; Tulloch et al., 2011); (Lemoine et al., 2018; Lind et al., 2017b; Tiburcy et al.,…”
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Cardiovascular disease models: A game changing paradigm in drug discovery and screening
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Metadata
- Authors
- MacQueen, L. A., Sheehy, S. P., Chantre, C. O., Zimmerman, J. F., Pasqualini, F. S., Liu, X., Goss, J. A., Campbell, P. H., Gonzalez, G. M., Park, S.-J., Capulli, A. K., Ferrier, J. P., Kosar, T. F., Mahadevan, L., Pu, W. T., & Parker, K. K.
- Affiliations
- Harvard University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Parker, Kevin Kit
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2018-07-23
- Volume
- 2
- Issue
- 12
- Pages
- 930-941
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC6774355
- OpenAlex
- W2884444313
- Semantic Scholar
- fe2a5e78ca3d5d351aa428f530fae947c66402fc
- Cited by
- 227
- References
- 84
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 27 · 2023: 30 · 2022: 41 · 2021: 34 · 2020: 35 · 2019: 21 · 2018: 2
- FWCI
- 23.91
- Type
- journal article
- Language
- en
- Update notices
- addendum (2022-03-08)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UH3TR000522)
- National Heart, Lung, and Blood Institute (UH3HL141798, UG3HL141798)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- left ventricle, nanofibrous scaffolds, cardiomyocytes, iPSC-derived cardiomyocytes, ejection fraction, pressure-volume loops, ventricular assist, bioreactors
- MeSH terms
- Animals, Arrhythmias, Cardiac, Extracellular Matrix, Heart Ventricles, Humans, Models, Biological, Myocardial Contraction, Polymers, Ventricular Function, Computer-Aided Design, Rats, Sprague-Dawley, Tissue Engineering, Myocytes, Cardiac, Rats, Tissue Scaffolds, Induced Pluripotent Stem Cells, Nanofibers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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