The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index; 59 of the 78 sources its claims cite were checked for support.
In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid
Open accessAbstract
RATIONALE: One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes-a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ. OBJECTIVE: To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle. METHODS AND RESULTS: We optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease. CONCLUSIONS: This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.
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Claims the paper makes
65 Own result · 30 Own interpretation · 16 No basis given · 14 Partly supported · 8 No full text of the sources · 6 Supported · 3 Couldn’t confirm · 2 Own method · 1 Supported so far · 1 Mixed support · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is now clear evidence from our group and the work of others that stem cell maturation and differentiation and the proper function of cells derived thereof are critically dependent on the temporal and spatial engagement of cell surface integrins with extracellular matrices (ECM) both in a given organ system during development19 and in the context of ex vivo stem cell culture20–27.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [19] source
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says integrin-mediated interactions are vital to normal cell function and differentiation, and the Results & Discussion report changes in integrin expression as human embryonic stem cells form definitive endoderm. The paper does not establish that maturation and the function of derived cells critically depend on the temporal and spatial engagement of integrins with ECM; it describes the proposed role of the observed integrins as requiring further investigation. (LLM, conf=0.84)
- Partly supportedcites [21] sourceExperimental — accuracy not yet measured
The Abstract and Discussion (page numbers not supplied) show that integrin engagement with fibronectin and vitronectin affects human embryonic stem-cell differentiation to definitive endoderm in culture. This supports the ex vivo differentiation part of the citation, but the paper does not establish dependence of later maturation or derived-cell function on temporal and spatial integrin–ECM engagement. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [22] source
- Not checked — no full text of the sourcecites [23] source
- Not checked — no full text of the sourcecites [24] source
- Partly supportedcites [25] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says extracellular substrates, including ECM, can guide ex vivo stem-cell growth and differentiation. The Results and Discussion (page unavailable) show that integrins largely mediate human ES-cell adhesion to ECM-coated surfaces. The paper does not establish that temporal and spatial integrin–ECM engagement is critical for maturation, differentiation, or derived-cell function; it also reports undifferentiated growth on surfaces that do not act through integrins. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [26] source
- Partly supportedcites [27] sourceExperimental — accuracy not yet measured
The paper’s Discussion (page not provided) reports that α5β1 integrin priming promotes osteogenic differentiation of cultured mesenchymal cells, supporting the claim’s ex vivo differentiation component. It does not establish that stem cell maturation or derived-cell function generally depends on temporal and spatial integrin–ECM engagement; its model promotes differentiation independently of the cell adhesion mediated by the peptide’s RRET sequence. (LLM, conf=0.85)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3D bioprinting.”
- Also stated in: § INTRODUCTION · hedged
“3D bioprinting has been proposed as a means to generate more geometrically complex tissues from the bottom-up.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Abstract > Rationale:
What the sources say
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
The Results and Discussion (Fig. 4; page unavailable) describe printing a complex embryonic chick-heart model in soft alginate, and the Methods identify atria and ventricles in the heart used to make the model. The paper describes a coronary arterial tree as a separate print (Fig. 3), not large vessels reproduced within the printed heart model. (LLM, conf=0.85)
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says bioprinting produces controlled 3D structures with defined biomaterial geometries. The Results and Discussion (page not provided) describe cylindrical cardiac patches, not models replicating a whole heart with chambers and large vessels. That specific anatomical claim is unsupported. (LLM, conf=0.86)
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
The 3D Printing section (page not provided) describes patient-specific heart models made from a printed scaffold infused with silicone and hydrogels to mimic myocardial tissue. The Segmentation and Digital Modeling section identifies structures including the aorta and ventricular septum, but the paper does not establish that the models replicate the heart’s full chamber-and-large-vessel structure. It describes 3D printing, not bioprinting. (LLM, conf=0.86)
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Abstract and 'FRE Printing 3D PDMS Structures' section describe printing complex structures from soft PDMS, including tubes and a bifurcation (page not specified in our copy). They do not report a heart model or a structure replicating the heart’s chambers and large vessels. (LLM, conf=0.85)
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The Methods (page unavailable) describe 3D-printed aortic models made with flexible resin, supporting the narrower point that flexible cardiac-anatomy models can be printed. They do not describe 3D bioprinting with soft biomaterials or a model of the heart with chambers and large vessels; the left atrium and ventricle were explicitly excluded. (LLM, conf=0.88)
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Development of Printing Materials section (page not provided) says PolyJet 3D printing can replicate complex cardiac anatomy using materials ranging from very soft to hard. The Future Directions section (page not provided) also discusses modeling vessel and chamber walls with material blends. The copy does not establish that 3D bioprinting, specifically, produces a model of the heart incorporating both chambers and large vessels from soft biomaterials. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [15] source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Current applications section describes 3D-printed models showing complex relationships among cardiac chambers and great arteries, and the 3D printing process section says some printers make soft, rubberlike models (page numbers unavailable). But the paper distinguishes those anatomical models from bioprinting, which it discusses in the Abstract and Future direction as a prospect for implants and tissue engineering. It does not say the described heart models are made by 3D bioprinting. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [17] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § INTRODUCTION · hedged
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The fact that macroscale contractile function has not yet been achieved in a 3D printed, perfusable, chambered heart model reflects the challenges associated with handling mature cardiac muscle cells.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The passage indexed as Abstract (page unavailable) says a fully functional 3D-bioprinted organ has not yet been achieved, and describes perfusable vasculature separately from a contracting ventricular model. But that model did show chamber-scale contraction, including a roughly 5% decrease in interior cross-sectional area. The paper therefore supports the absence of a demonstrated combination of perfusion and contraction in its own chambered model, not an unqualified claim that macroscale contraction has not been achieved. (LLM, conf=0.83)
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
In Results and Discussion (page not available), the paper describes a macroscale heart-shaped alginate print with anatomical detail, while perfusion is demonstrated in a separate printed coronary arterial tree. This supports that the paper did not demonstrate a perfusable, contracting chambered heart model, but it does not establish the broader claim that no such model had yet been achieved. (LLM, conf=0.82)
- Supportedcites [18] source
In Results and Discussion (page unavailable), the paper describes a small-scale printed heart with perfusable vessels and distinct ventricular chambers, but treats it as a proof of concept. It says further cultivation and muscle-bundle maturation are essential to generate a functional organ; contraction is demonstrated for the separate cardiac patches, not the chambered heart. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Yet, inclusion of contiguous, living muscle to support pump function has not been achieved.”
- Also stated in: § INTRODUCTION · plain
“The fact that macroscale contractile function has not yet been achieved in a 3D printed, perfusable, chambered heart model reflects the challenges associated with handling mature cardiac muscle cells.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Abstract > Rationale:
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The ventricle-model passage (section labeled Abstract; page unavailable) reports a viable, dense layer of interconnected cardiomyocytes that contracted and reduced the chamber’s cross-sectional area. The concluding passage says a fully functional bioprinted organ has not yet been achieved, but the paper does not establish that contiguous living muscle has not been included in a bioprinted heart model. (LLM, conf=0.84)
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
In Results and Discussion, the printed heart is described as a fluorescently labeled alginate model made from an image of a fixed embryonic chick heart, not a living, pumping construct. This supports the limitation for this paper’s heart model, but the paper does not establish the broader claim that no bioprinted heart model has achieved contiguous living muscle supporting pump function. Page numbers are not available in our copy. (LLM, conf=0.82)
- Supportedcites [18] source
In Results and Discussion (page not available), the paper reports a printed, cellularized heart but says that proper assembly of muscle bundles remains a goal for future cultivation and is essential to a functional organ. It demonstrates anatomical compartments and perfusion, not muscle-driven pump function. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § INTRODUCTION · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In fact, the only 3D printed, volume-holding structure to successfully demonstrate cardiac function is a single ventricle model.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The paper’s ventricle-model passage (labeled Abstract in our copy; no page given) describes a printed chamber that maintained its shape and contracted. A later passage reports a decrease in its interior cross-sectional area during contraction. These passages support the functional single-ventricle example, but do not establish that it was the only 3D-printed volume-holding structure to demonstrate cardiac function. (LLM, conf=0.84)
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Specifically, Lee et al., printed a support material (i.e., type I collagen) as a “shell” that is filled with cardiomyocytes in a fibrinogen suspension at a concentration of 300 million cells per milliliter8.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The ventricle description (section labeled Abstract; page not provided) supports the use of collagen as a structural shell around a core containing cardiomyocytes. It describes a high-density cell bio-ink but does not specify a fibrinogen suspension or a concentration of 300 million cells per milliliter. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the 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.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Supportedcites [6] source
The Results (‘Bioengineering hvCOC’; page unavailable) describe a simplified hollow ventricular chamber formed from cardiomyocytes mixed with scaffold materials. The Methods (‘hvCOC generation’; page unavailable) specify that this cell-laden mixture was placed in a mold and gelled, supporting the casting method attributed to this source. The separate claim about seeding cardiomyocytes after fabrication is attached to citation 7, not this paper. (LLM, conf=0.88)
- Supportedcites [7] source
Citation 7 is attached to the seeding-after-fabrication part of the sentence, not the gel-casting part. The Introduction (page unavailable) says the authors fabricated ellipsoidal, thin-walled ventricle chambers and then seeded them with cardiomyocytes; the Methods section on ventricle seeding describes adding cells to the completed scaffolds. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Ultimately, we employed freeform reversible embedding of suspended hydrogels9, 12 with success, wherein our embedding material or “slurry” consisted of gelatin microparticles.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Bioprinted chambered cardiac mimic with large vessel extensions exhibits high fidelity to the digital template.
What the sources say
- Supportedcites [9] source
The Results and Discussion section describes FRESH printing with a support bath made of gelatin microparticles. The Materials and Methods section confirms that the gelatin slurry was used for FRESH printing. The citing authors’ statement that they used it successfully describes their own work, not a result attributed to this source. (LLM, conf=0.92)
- Supportedcites [12] source
The Introduction identifies freeform reversible embedding of suspended hydrogels (FRESH) as a process using a gelatin microparticulate slurry to print soft hydrogels. The citing authors’ statement that they used it successfully in the remainder of their own study is not attributed to this source. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“similar to results reported by MacQueen et al., we show that the hChaMP can respond to a range of isoproterenol doses7.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Advances to the Field.
What the sources say
- Supportedcites [7] source
In “Intra-ventricular pressure and volume measurements” (page not provided), MacQueen et al. report that their engineered ventricles showed a positive beat-rate response across isoproterenol concentrations from 0.1 nM to 0.1 mM. This supports the comparison to the hChaMP’s response across a range of doses; the paper does not itself study the hChaMP. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These measurements are on par with data shown in single ventricle models6, 7.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
What the sources say
- Supportedcites [6] source
The Results (‘Pump performance of hvCOC’) report an ejection fraction of 2.44 ± 0.27% for 25 miniature ventricle-like chambers. The cited paper therefore supplies ejection-fraction data for a single-ventricle model; the comparison with hChaMP is the citing authors’ own. (LLM, conf=0.87)
- Supportedcites [7] source
The paper’s “Intra-ventricular pressure and volume measurements” section reports ejection fractions for its rat and human engineered single-ventricle models. It supplies the comparison data cited by the hChaMP authors; the comparison with hChaMP is the citing authors’ own assessment. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
- It may state two separate claims as one. 41
- Probably not a substantial claim. 10
- The quote only partly states this claim. 1
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the 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.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Advances to the Field.
What the sources say
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
The Materials and methods describe functional testing of this paper’s ventricular chamber after 10–12 days in culture, which supports it as an example of a model characterized around two weeks. The Discussion also describes improved function with culture extended to day 20. Neither passage establishes that most comparable models were characterized only up to two weeks; the six-week result is the citing authors’ own finding, not a claim attributed to this source. (LLM, conf=0.75)
- Supportedcites [7] sourceExperimental — accuracy not yet measured
The Tissue-engineered ventricle chamber section says this model’s experiments were conducted 14 days after seeding, supporting its use as an example of a comparable model characterized at about two weeks. The citing authors’ six-week finding is their own result, not a claim attributed to this source. (LLM, conf=0.90)
- Disputedcites [8] sourceExperimental — accuracy not yet measured
The source’s ventricle-model passage (indexed as Abstract; no page supplied) says its printed ventricles were cultured for up to 28 days, not only two weeks. It does not establish how long most other models were characterized, and the citing authors’ six-week result is their own finding rather than one attributed to this source. (LLM, conf=0.78)
Checked by a reasoning model — may be wrong.
- Supportedcites [18] sourceExperimental — accuracy not yet measured
The citation is attached to the comparison with earlier models, not to the citing authors’ six-week hChaMP result. In the cited paper’s Results and Discussion (page unavailable), the printed cardiac patch is characterized on day 7, making it an example of a comparable model assessed within two weeks. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Supportedcites [6] source
The Introduction describes a fluid-ejecting human ventricle-like chamber and direct measurement of pressure-volume relationships. The Results section, ‘Pump performance of hvCOC,’ reports cyclical pressure and volume changes, reconstructed pressure-volume loops, and stroke volume, supporting the claim that the model handles volume and reproduces key heart pump dynamics. (LLM, conf=0.94)
- Supportedcites [7] source
The Abstract reports tissue-engineered left-ventricle models with measurable chamber volume and pressure-volume loops. The Intra-ventricular pressure and volume measurements section describes catheter measurements and PV loops during contraction cycles in both rat-cell and human-cell model ventricles, supporting the claim that these models reproduce pressure-volume dynamics, albeit at much smaller functional magnitudes than native hearts. (LLM, conf=0.92)
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The ventricle-model passage (labeled Abstract in our copy; no page given) reports a contracting printed chamber whose cross-sectional area decreased by up to about 5% at peak systole. This supports a cardiac model with changing chamber dimensions, but the paper does not show that it recapitulated the heart’s pressure-volume dynamics. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, these tissues are limited to a single ventricle model and thus lack the capacity for perfusion.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe a simplified, single ventricle-like chamber, supporting the single-ventricle part of the claim. The Discussion contrasts the model with native heart tissue that has integrated vasculature, but the paper does not establish that being a single-ventricle model causes a lack of perfusion capacity. The Results also report that the chamber pumps fluid, so lack of perfusion should not be read as lack of fluid movement. (LLM, conf=0.82)
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Model assumptions section describes a single left-ventricle model with an unvascularized wall, supporting the lack of vascular tissue perfusion. But the Bioreactor section reports fluid flow through the ventricle and demonstrates assisted, valve-directed pumping. The paper therefore does not support the broader claim that a single-ventricle model lacks perfusion capacity altogether. (LLM, conf=0.85)
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The ventricle-model passage (labeled Abstract in our copy; page unavailable) describes a printed left ventricle, supporting the single-ventricle part. It does not establish that this model lacks the capacity for perfusion. A separate passage under the same label reports successful perfusion of a printed vascular network, though not of the ventricle model. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Early engineered heart tissues consisted of geometrically simple structures (strips or rings) made by casting cardiomyocytes in an extracellular matrix-based gel1–3.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [1] source
- Not checked — no full text of the sourcecites [2] source
- Supportedcites [3] source
The Abstract describes casting neonatal rat cardiac myocytes with collagen I and matrix factors in circular molds to form ring-shaped engineered heart tissue. The Engineered Heart Tissue section gives the casting procedure, and the Abstract contrasts these rings with earlier lattices. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Multiple studies have demonstrated the capacity to print entire heart organ models using biological materials, but the resulting constructs have either lacked cells8, 9 or evidence of electromechanical function18.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Supportedcites [8] source
The Abstract describes a neonatal-scale human heart printed from collagen and assessed for anatomical fidelity, not electromechanical function. It reports contractions and electrical propagation in separately printed ventricles, so those results do not establish electromechanical function in the entire heart model. (LLM, conf=0.92)
- Supportedcites [9] source
The Results and Discussion section reports printing a whole embryonic chick heart model in alginate and assesses its anatomical fidelity, not electromechanical function. The cells stained for imaging belonged to the original heart used to make the model; the printed construct is described as alginate, with no cells reported. (LLM, conf=0.90)
- Supportedcites [18] source
The Results and Discussion (page not specified) describe small-scale, cellularized hearts printed with biological bioinks, but report anatomical structure and perfusability rather than electromechanical function for those hearts. The authors say future cultivation and electromechanical cues are needed for the printed organ to mature. The functional measurements reported elsewhere concern cardiac patches, not the whole-heart constructs. (LLM, conf=0.90)
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The concept is gaining traction, as the ability to print tissues composed entirely of native proteins, cells and/or biocompatible synthetic components is possible and accessible to many laboratories9–17.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
The Results and Discussion (page unavailable) demonstrate printing biological structures from natural biopolymers and describe a low-cost FRESH setup intended to make bioprinting accessible to more laboratories. But the authors say that directly bioprinting functional tissues and organs still requires further development; they anticipate broader laboratory access rather than establish that it has already been achieved. (LLM, conf=0.86)
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
The Conclusions (page not provided) report successful bioprinting of a cardiac patch made with extracellular matrix, progenitor cells, and gelatin methacrylate. This establishes that such printing is possible, but the paper does not establish that it is accessible to many laboratories. (LLM, conf=0.86)
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
The 3D Printing section (page not provided) describes making a heart model from a proprietary scaffold, silicone, and hydrogels, supporting the narrower point that tissue-like models can be printed. It does not establish that the model is tissue composed of native proteins or cells, that its synthetic components are biocompatible, or that this process is accessible to many laboratories. (LLM, conf=0.83)
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
The Introduction describes PDMS as a biocompatible biomaterial, and the paper demonstrates printing PDMS structures. The Abstract says its low-cost, open-source approach can be rapidly implemented for research applications. It does not demonstrate printing tissues composed entirely of native proteins, cells, or synthetic components, or establish that tissue printing is accessible to many laboratories. (LLM, conf=0.86)
- Could not verifycites [13] sourceExperimental — accuracy not yet measured
The Methods (Creation of 3D Models and Valves; page unavailable) describe printing anatomical models in flexible resin and hard plastic, not printing tissues. A search of our copy for native proteins, cells, biocompatible components, and laboratory accessibility found no passage addressing whether such tissue printing is possible or accessible to many laboratories. (LLM, conf=0.74)
- Could not verifycites [14] sourceExperimental — accuracy not yet measured
The Printing Technology and Development of Printing Materials sections describe synthetic materials used to print anatomical models that approximate cardiac tissue properties. They do not address printing tissues made of native proteins or cells, whether the synthetic components are biocompatible, or whether such printing is accessible to many laboratories (searched: native proteins, cells, bioprinting, laboratories). (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [15] source
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Future direction section (page unavailable) says 3D printing has been used experimentally for tissue engineering, with cells placed on a printed scaffold. It does not establish that tissues composed entirely of the listed components can be printed or that this is accessible to many laboratories; the Current limitations section (page unavailable) instead describes expensive equipment and potentially prohibitive costs for small programs. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [17] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Finally, fibronectin/integrin β1/β−catenin signaling promotes the emergence of mesoderm from induced pluripotent stem cells.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says fibronectin signals through integrin-β1 and stimulates Wnt/β-catenin signaling to promote mesodermal fate. However, the Materials and Methods identify the cells studied as mouse embryonic stem cells, not induced pluripotent stem cells; the claimed cell type is unsupported. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This study was the first to establish a direct link between elements of the focal adhesion, namely integrin-linked kinase (ILK), with GSK3β29, the primary antagonist of β-catenin.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results (page unavailable, Fig. 4D) report that Gsk3β co-immunoprecipitated with ILK, supporting a link between them. The paper does not establish that it was the first study to find that link, and co-immunoprecipitation alone does not establish direct binding. (LLM, conf=0.84)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“suggesting the elastic nature of the gels with a stiffness similar to that of the late embryonic heart31.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
What the sources say
- Partly supportedcites [31] sourceExperimental — accuracy not yet measured
The Results and Discussion section reports that embryonic hearts behave elastically and stiffen to neonate and adult heart stiffness by embryonic day 14 (page unavailable). It does not describe 10G0.25CFL gels or measure their elasticity or stiffness, so it cannot establish the claimed similarity. (LLM, conf=0.83)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“which will engage at least integrins α1β1 and α2β1, which are highly expressed in iPSC-derived cardiomyocytes38.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Recapitulating Cell-ECM interactions to facilitate proliferation and differentiation.
What the sources say
- Could not verifycites [38] sourceExperimental — accuracy not yet measured
The Introduction and Results describe gene-expression profiling of hiPSC-derived cardiomyocytes, but the passages retrieved for integrins α1β1 and α2β1, ITGA1/ITGA2/ITGB1, and type III collagen do not address those integrins’ expression or collagen binding. Our copy therefore does not verify the claim attributed to this paper. (LLM, conf=0.76)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“iPSC-derived cardiomyocytes express a myriad of MMPs including 1–3, 10, 11, 14–16 and 1938, as do hiPSC-derived smooth muscle cells, which were present, albeit more rarely in the hChaMP.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Recapitulating Cell-ECM interactions to facilitate proliferation and differentiation.
What the sources say
- Could not verifycites [38] sourceExperimental — accuracy not yet measured
The Results section on emerging cellular heterogeneity reports gene-expression profiles in hiPSC-derived cardiomyocytes, but does not identify the claimed MMPs. Searches for MMP19, the listed MMP genes, and matrix metalloproteinases found no supporting passage in our copy. The claim about smooth muscle cells and hChaMP is likewise not addressed. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“the pressure generated by the hChaMP, while low (0.23 mmHg), is higher than other reported values6, 7.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Advances to the Field.
What the sources say
- Supportedcites [6] source
The Results section (Pump performance of hvCOC) reports a developed pressure of 1.26 ± 0.12 mmH₂O, approximately 0.093 mmHg. That is lower than the citing paper’s 0.23 mmHg value, so this source supports the comparison to a previously reported value; it does not itself report the hChaMP measurement. (LLM, conf=0.91)
- Supportedcites [7] source
The citation is attached to the comparison with previously reported pressures, not to the citing study’s own hChaMP measurement. In “Intra-ventricular pressure and volume measurements,” MacQueen et al. report a chamber-pressure difference of about 50 μmHg (0.05 mmHg), which is lower than 0.23 mmHg. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“only α6β1 has been reported to promote pluripotency37, while all others appear to promote differentiation in an ECM type-specific manner.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Recapitulating Cell-ECM interactions to facilitate proliferation and differentiation.
What the sources say
- Partly supportedcites [37] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) supports a role for α6β1 in maintaining human pluripotent stem-cell self-renewal. It does not support the claim that all other integrins promote ECM-specific differentiation: the Introduction says their roles remain incompletely understood, and the paper’s reference list identifies a study of self-renewal via αVβ5. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > In situ differentiation to enhance cell density and tissue connectivity.
What the sources say
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
The Results section (Bioengineering hvCOC; page unavailable) reports a wall thickness of approximately 100 μm. It does not compare that thickness with prior wall-thickness values or establish that thicker hChaMP walls exceed existing tissue models. The cited paper also studies hvCOCs, not the citing document’s hChaMPs. (LLM, conf=0.78)
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
In “Model assumptions for tissue-engineered ventricle chambers” (page unavailable), MacQueen et al. describe a tissue-engineered ventricle designed with a wall thickness limited to approximately 0.1 mm, providing a prior thin-wall benchmark. The paper does not establish that the thickest hChaMP walls exceed existing tissue models, so it supports only the low-end comparison. (LLM, conf=0.76)
- Partly supportedcites [8] sourceExperimental — accuracy not yet measured
The passage on the FRESH-printed coronary artery tube (section labeled Abstract; no page given) reports a wall thickness of approximately 300 μm, providing a prior-literature benchmark for thin printed walls. It does not give the hChaMP thickness range or establish that its thickest walls greatly exceed existing tissue models. (LLM, conf=0.78)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“hChaMPs demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Abstract > Methods and Results:
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Abstract > Methods and Results:
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“However, in some cases the spontaneous source of depolarization could be overcome and the directionality of propagation altered via electrical point stimulation at another location within the hChaMP”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“We found, according to design, that all of the ink formulations fell within the range of 10–40 cP, ensuring low pressure requirements (28–38 kPa) with printing.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“We found that differentiation outcomes not only corresponded to the GelMA fraction, but also were largely dependent on the addition of fibronectin and laminin (Table 1, Figure 2d, e).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“hChaMPs could be routinely fabricated such that macroscale beating was observed (Online Video V).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“For the crosslinked gels of this specific formulation, the storage modulus (G’, 6.14 ± 1.13 kPa) was nearly two orders of magnitude higher than the loss modulus (G”, 0.09 ± 0.06 kPa)”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Particles of approximately 100 μm could support printing of the chambered cardiac mimic with intact chambers, patent large vessels, and material properties conducive to handling (Online Video III).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Bioprinted chambered cardiac mimic with large vessel extensions exhibits high fidelity to the digital template.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Material handling was difficult below 10% GelMA as final structures were flimsy and easily damaged; whereas printability was difficult to accomplish above 15% GelMA as extrusion required high pressures which made material control difficult and which sometimes resulted in cell damage.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Intracellular machinery associated with the sarcolemma and sarcoplasmic reticulum was also well expressed and appropriately organized (Figure 5c).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs express and localize proteins consistent with a maturing cardiomyocyte phenotype.
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Contractile performance was not enhanced over time but did not decline significantly either”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“and the thickness of the wall was typically between 100 μm and 500 μm with the thickest region exceeding 500 μm (Figure 4e).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hiPSCs 3D printed in an optimized bioink give rise to a contiguous muscle wall to form a human chambered muscle pump (hChaMP).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Bioink could be discerned in the inner portion of the hChaMP wall, but was largely without cells (Figure 4e, white oval).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hiPSCs 3D printed in an optimized bioink give rise to a contiguous muscle wall to form a human chambered muscle pump (hChaMP).
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, this formulation achieved a cell density of 0.1 mg DNA/g of gel, which is on the same order of magnitude of native cardiac tissue, (~0.3 mg DNA/g of myocardial mass) and significantly higher than the condition that produced the lowest amount of differentiation32”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
What the sources say
- Not checked — no full text of the sourcecites [32] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“To address this hurdle, we developed an approach that involved backfilling an inverted geometry made of sacrificial ink; however, low cell viability and low proliferation associated with the sacrificial ink limited further use”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Bioprinted chambered cardiac mimic with large vessel extensions exhibits high fidelity to the digital template.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Sarcoplasmic reticulum ATPase2a (SERCA2a) exhibited signal in the majority of cells, with staining in close apposition to the myofibrils (1.50 ± 0.19% of cTnT area).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs express and localize proteins consistent with a maturing cardiomyocyte phenotype.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“By Day 14, approximately 90% of the bioink volume was populated with cells, both singular and in large colonies, with 40% ± 11% corresponding to colony area (Figure 4a).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hiPSCs 3D printed in an optimized bioink give rise to a contiguous muscle wall to form a human chambered muscle pump (hChaMP).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“but smooth muscle cells (10.5 ± 4.2% of cells via staining for alpha smooth muscle actin, αSMA) and endothelial cells (4.2 ± 2.4% of cells via staining for CD31) were present in hChaMPs.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hiPSCs 3D printed in an optimized bioink give rise to a contiguous muscle wall to form a human chambered muscle pump (hChaMP).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The end result is a living pump that mimics the chambers and large vessel conduits of a native heart while housing viable, densely packed and functional cardiomyocytes (Figure 1).”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 usual volume moved through the chambers was 0.5 μL and maximum volume moved through the chambers was 5.0 μL”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This critical expansion phase enabled final cell densities (~0.1 mg DNA/g of hChaMP) of the same order of magnitude as native tissue (~0.3 mg DNA/g of myocardial mass)32.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > In situ differentiation to enhance cell density and tissue connectivity.
What the sources say
- Not checked — no full text of the sourcecites [32] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“we calculated an ejection fraction of 0.7% on average, with a maximum value of 6.5%”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“as colonies grew, it appeared that either ECM hydrolysis or direct remodeling of ECM via matrix metalloproteinases (MMPs) occurred to provide space, as hiPSCs expressed MMPs 1, 5, and 6”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Recapitulating Cell-ECM interactions to facilitate proliferation and differentiation.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To support differentiation, the bioink should ideally contain integrin-binding motifs that enhance signaling associated with cardiomyocyte-specific differentiation.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This process requires the disruption of previously formed cell-cell connections, and a cell strainer is required to remove aggregated cardiomyocytes, which further adds to the total number of cardiomyocytes that must be produced prior to printing.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“3D bioprinting has been proposed as a means to generate more geometrically complex tissues from the bottom-up.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the same time, the lack of geometrical complexity limits the utility of the model for in vitro study of cardiac function and disease, as these tissues can generate force but do not pump fluid.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As one of many examples, mesoderm specification has been linked to α5β1 integrin activation.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [26] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“hChaMPs were neither perfused in a bioreactor, exposed to controlled, resistive mechanical stimulation, nor exposed to electrical stimulation; all factors shown to improve maturation.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs express and localize proteins consistent with a maturing cardiomyocyte phenotype.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, engagement of fibroblast-derived ECM via β1, α2, and α3 integrins in human embryonic stem cells activates the Wnt/β-catenin pathway via the MEK-ERK pathway, which drives endoderm differentiation28.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [28] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggestive of advanced maturation in the hChaMP.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs express and localize proteins consistent with a maturing cardiomyocyte phenotype.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting electrical stimulation can promote connectivity and further enhance the concerted function of the hChaMP.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stroke work and ejection fraction are on par with existing systems”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Advances to the Field.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — 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 experimentally determined stroke volume is slightly lower than this, likely due to an uneven distribution of cardiomyocytes across the hChaMP surface.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hChaMPs exhibit contiguous electrical function and pump dynamics.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as our in silico model demonstrated, increasing the cell layer thickness should increase the volume output of the hChaMP, resulting in more robust pump function”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > DISCUSSION > Advances to the Field.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This important outcome was made possible by an optimized bioink that allowed extensive stem cell proliferation prior to differentiation to yield contiguous muscle walls of up to 500 μm in thickness.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Conclusion.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This approach could be applied to many other cell types with poor proliferative and migratory capacity following differentiation.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Conclusion.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
Cardiomyocytes do not proliferate or migrate readily.
“More specifically, cardiomyocytes do not proliferate or migrate readily.”
The paper relies on this without support.
A high cell density is required for the formation of functional cell-cell junctions.
“it is challenging to achieve the high cell density required for the formation of functional cell-cell junctions while maintaining the structural support needed for an enclosed chamber.”
The authors state this as an assumption.
The pipetted disk used for cell-density estimation has a thickness of 1 mm.
“Assuming a disk thickness of 1 mm”
The authors state this as an assumption.
The average cell contains 6 pg of DNA.
“If the average cell contains 6 pg of DNA”
The authors state this as an assumption.
In the in silico model, the entire wall thickness is occupied by cells.
“1) the entirety of the wall thickness is occupied by cells”
The authors state this as an assumption.
In the in silico model, about half of the wall thickness, 600–650 μm, is occupied by cells.
“2) approximately half of the wall thickness (600–650 μm) is occupied by cells”
The authors state this as an assumption.
In the in silico model, cellularization is confined to the outer 200–250 μm of the structure.
“3) the cellularization is limited to the outer 200–250 μm of the structure”
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
“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 Kupfer et al., 2020
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
“As a result, bridging the length scales from the micro- and nanometer scale to the centimeter scale to induce both intra- and intercellular organization within engineered heart models remains a major challenge in 3D printing functional organs and tissues32, 34, 35.”
From Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles (2023) · cites this paper as [32]
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 Kupfer et al., 2020
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
“Existing models span a wide range - from approximately 174,000 cells per ECC to about 15 million cells - directly influencing both production cost and feasibility (Lee et al., 2008; Chang et al., 2022; Kupfer et al., 2020).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Kupfer et al., 2020
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
“More sophisticated fabrication strategies, including nanofabrication and 3D (bio)printing, offer greater control over geometry and microstructure but raise concerns about efficiency, cost, and throughput (Lee et al., 2019; Kupfer et al., 2020; Esser et al., 2023).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Kupfer et al., 2020
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
“Alternatively, bioprinting of a cardiac chamber may offer a higher structural complexity.However, inherent limitations in the resolution of this technique often yield poor-quality dense cardiac constructs incapable of beating co-ordinately unless hPSCs are expanded and differentiated to CMs within a printed structure (Kupfer et al., 2020).”
From A human engineered mini-heart platform for mimicking ventricular pump function (2025) · cites this paper as Kupfer et al., 2020
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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 [32]
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 [39]
The cited source says what the claim attributes to it.
In the citing paper
“Nonetheless, Kupfer et al., Chang et al. and Choi et al. reported volumetric performance data, with Kupfer et al. additionally demonstrating Pressure Difference (ΔP) measurements (Kupfer et al., 2020; Chang et al., 2022; Choi et al., 2023).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Kupfer et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“While Patel and Birla present a single chamber with an inlet and outlet (Patel and Birla, 2017), the Kupfer et al. model stands out by using bioprinting to create a more complex perfusable structure, although it lacks valve integration (Kupfer et al., 2020).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Kupfer et al., 2020
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 Kupfer et al., 2020
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 Kupfer et al., 2020
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 Kupfer et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
“fibronectin, laminin-111, and collagen methacrylate”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > Optimization of a bioink supportive of hiPSC proliferation and differentiation.
“95 μg/mL laminin-III (LN)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > Conclusion.
“contiguous muscle walls of up to 500 μm in thickness.”
§ In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid > RESULTS > hiPSCs 3D printed in an optimized bioink give rise to a contiguous muscle wall to form a human chambered muscle pump (hChaMP).
“the thickness of the wall was typically between 100 μm and 500 μm with the thickest region exceeding 500 μm”
Citations
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Human cardiovascular organoids: Biomedical applications and ethical challenges
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Progressive developmental cues from multiple cardiac cell types promote cardiomyocyte maturationPreprint
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“…both positive and negative - to cardioactive compounds such as isoproterenol, nifedipine, vasopressin, carbachol, and phenylephrine (Lee et al., 2008; Li et al., 2018; Keung et al., 2019; MacQueen et al., 2018; Kupfer et al., 2020; Esser et al., 2023; Kuckelkorn et al., 2025; Ribeiro et al., 2025).”
InfluentialCardiac Tissue Engineering: A Pathway for Repair
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Challenges and opportunities for cardiac organoids: A comprehensive review
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Metadata
- Authors
- Kupfer, M. E., Lin, W.-H., Ravikumar, V., Qiu, K., Wang, L., Gao, L., Bhuiyan, D. B., Lenz, M., Ai, J., Mahutga, R. R., Townsend, D., Zhang, J., McAlpine, M. C., Tolkacheva, E. G., & Ogle, B. M.
- Affiliations
- University of Minnesota (US)
- University of Alabama at Birmingham (US)
- ORCID
- Venue
- Circulation Research
- Published
- 2020-07-03
- Volume
- 127
- Issue
- 2
- Pages
- 207-224
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC8210857
- OpenAlex
- W3014021096
- Cited by
- 329
- References
- 64
- Citations by year
- 2026: 45 · 2025: 55 · 2024: 63 · 2023: 51 · 2022: 58 · 2021: 47 · 2020: 10
- FWCI
- 13.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL137204, R01HL149137, R01HL131017)
- National Institute of General Medical Sciences (T32GM008347)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079626)
- National Institute of Biomedical Imaging and Bioengineering (DP2EB020537)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- 3D bioprinting, human induced pluripotent stem cells, cardiomyocyte differentiation, in situ differentiation, bioinks, extracellular matrix, electromechanical coupling, action potential propagation, cardiac tissue engineering, cardiac remodeling, tissue grafting
- MeSH terms
- Action Potentials, Cell Differentiation, Cells, Cultured, Humans, Myocardial Contraction, Organoids, Extracellular Matrix Proteins, Tissue Engineering, Myocytes, Cardiac, Cell Proliferation, Induced Pluripotent Stem Cells, Bioprinting
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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