The DOI matches its Crossref record; 129 of the 131 references it cites were found in a registry or an index, and 2 are not checked yet; 44 of the 86 sources its claims cite were checked for support.
Modeling Physiological Events in 2D vs. 3D Cell Culture
Open accessAbstract
Cell culture has become an indispensable tool to help uncover fundamental biophysical and biomolecular mechanisms by which cells assemble into tissues and organs, how these tissues function, and how that function becomes disrupted in disease. Cell culture is now widely used in biomedical research, tissue engineering, regenerative medicine, and industrial practices. Although flat, two-dimensional (2D) cell culture has predominated, recent research has shifted toward culture using three-dimensional (3D) structures, and more realistic biochemical and biomechanical microenvironments. Nevertheless, in 3D cell culture, many challenges remain, including the tissue-tissue interface, the mechanical microenvironment, and the spatiotemporal distributions of oxygen, nutrients, and metabolic wastes. Here, we review 2D and 3D cell culture methods, discuss advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.
Verified 2026-10-07 · 2 references not checked yet
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
44 of 86 cited sources checked · 18 supported · 1 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“These behaviors include cell differentiation, migration, growth, and mechanics, all of which are impacted by their biochemical and biomechanical microenvironment (57).”
§ 2D vs. 3D Cell Culture > Abstract
What the sources say
- Supportedcites [57] source
In “Microengineering Meets Cell Biology” (page not provided), the paper says the mechanical environment is critical for cell growth and tissue differentiation, and describes chemical gradients used to study cell motility. The same section describes how ECM patterning and substrate conditions affect cell shape and tissue contraction, supporting the claim about mechanics. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“For instance, some important characteristics of cancer cells cannot be appropriately modeled in 2D cultures (22).”
§ 2D vs. 3D Cell Culture > Abstract
What the sources say
- Could not verifycites [22] sourceExperimental — accuracy not yet measured
The Experimental Section describes culturing NIH-3T3 fibroblasts in porous beads, and the paper’s discussion of three-dimensional matrices concerns cell viability. Searches for cancer cells and comparisons with 2D cultures found no passage addressing whether 2D cultures inadequately model cancer-cell characteristics; page numbers were not available in our copy. (LLM, conf=0.74)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Results from 3D studies demonstrate that increasing the dimensionality of extracellular matrix (ECM) around cells from 2D to 3D can significantly impact cell proliferation, differentiation, mechano-responses, and cell survival (2,10,41).”
§ 2D vs. 3D Cell Culture > Abstract
What the sources say
- Not checked — no full text of the sourcecites [2] source
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
The Introduction (page not provided) reports that 3D matrices can alter cell phenotype and metabolism and discusses proliferation, differentiation, and resistance to toxic effects. It does not address mechano-responses. The Discussion (page not provided) also states that this study found no evidence that moving cells from 2D plastic to 3D collagen affected their health or viability, so the paper does not support the full list as a finding of this study. (LLM, conf=0.84)
- Partly supportedcites [41] sourceExperimental — accuracy not yet measured
The Results (§3.3; page unavailable) show that cells remained viable and proliferated on the 3D GelMA scaffolds. The Introduction (§1) discusses scaffold cues affecting differentiation, but the paper does not establish that changing the ECM from 2D to 3D significantly changes all four listed outcomes; its mechanical measurements concern the scaffolds, not cellular mechano-responses. (LLM, conf=0.84)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The sandwich culture method, e.g., placing cells between two layers comprised of ECM, polyacrylamide, or collagen, has long been demonstrated to produce hepatocyte cell cultures, where morphology and function more accurately reproduce in vivo behavior (9,29,34,65,73).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Not checked — no full text of the sourcecites [9] source
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The opening summary (p. 1043) reports that rat hepatocytes between two collagen layers maintained albumin mRNA at levels similar to normal liver, supporting the claim about preserved function. The paper does not demonstrate that sandwich cultures reproduce in vivo morphology more accurately, and it tests collagen rather than the other materials listed in the citing sentence. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [34] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cells in our body perform bioactivities in response to the stimulation from a highly complex, 3D microenvironment (15,98,112).”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Supportedcites [15] source
The Biomimetic Approach section says that cells in living organisms inhabit a biologically complex microenvironment, respond to its molecular and physical cues, and remodel it. It contrasts this native context with standard 2D culture and describes the relevant in vivo environment as dynamic and 3D. (LLM, conf=0.94)
- Partly supportedcites [98] sourceExperimental — accuracy not yet measured
The Results (Cell interactions with scaffolds; page unavailable) show that endothelial-cell infiltration responds to porosity, RGD peptide, and S1P delivery in three-dimensional engineered scaffolds. This supports the general idea that a cell’s surroundings influence its activity, but the paper does not establish the broader claim about cells throughout the body responding to a highly complex natural 3D microenvironment. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [112] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The introduction of 3D cell culture approaches aimed at modeling the in vivo interactions of tissues and organs has opened new possibilities in studying the underlying biochemical and biomechanical signals (46,57).”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Supportedcites [46] source
The “Biomaterials to create 3D tumor models” section says 3D cultures better resemble tumors in vivo and help researchers understand cancer biology. Its subsections describe using 3D models to study cellular interactions, soluble microenvironmental cues, and matrix mechanics; “Future directions and considerations” also discusses organ-on-chip models. The paper supports the claim in the context of cancer models. (LLM, conf=0.87)
- Supportedcites [57] source
The “3D Cell Culture” section describes a new wave of 3D models designed to mimic organ structure, mechanical properties, and biochemical functions. In “From 3D Culture to Organs-on-Chips,” the paper says these microengineered approaches opened new possibilities for modeling organ-level structures and incorporating mechanical and chemical signals. The claim is supported as a description of these advanced 3D approaches, rather than conventional gel cultures. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This device was able to maintain spheroid cultures for up to 2 wk (110).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Partly supportedcites [110] sourceExperimental — accuracy not yet measured
The Results and discussion section, under “Long-term culture of spheroids in hanging drops” (page unavailable), reports viable spheroids after 12 days of culture. This supports long-term maintenance with the device, but the copy does not establish the claimed two-week (14-day) duration. (LLM, conf=0.85)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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
“Hepatocytes in the liver are surrounded by a complex ECM, and several researchers have shown that conventional 2D culture methods, flasks with or without ECM protein coatings, do not establish well enough the complex microenvironment that hepatocytes need to function (29,34,73).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Supportedcites [29] source
The Introduction (p. 1043) says hepatocytes rapidly degenerate under classical culture conditions and that adding complex extracellular matrix can prolong their function. The Results (p. 1046) show that albumin mRNA declined rapidly on a single collagen-gel layer but was maintained in collagen-sandwich culture, supporting the claim that conventional flat cultures inadequately sustain hepatocyte function. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [34] source
- Not checked — no full text of the sourcecites [73] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“This induced polarity may alter the functions of native cells with regard to spreading, migrating, and sensing soluble factors and other microenvironmental cues (61).”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Could not verifycites [61] sourceExperimental — accuracy not yet measured
The ‘Engineered microenvironments regulate LA/C-C epitope accessibility’ section reports that substrate properties affect cell spreading and nuclear-lamina polarization. The ‘Physiological implications’ section links that polarization to engineered niches, but neither section says that induced polarity in pseudo-3D models alters native-cell spreading, migration, or sensing of soluble factors and other cues. Searches for pseudo-3D models, migration, and soluble-factor sensing did not locate such a passage. (LLM, conf=0.73)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
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
“To control cell shape in 2D cell culture, micro-patterned substrates, such as cell-adhesive islands (30), microwells (121), and micropillars (40), have been created to customize the 2D shape of cells and help study the effects of cell shape on bioactivities.”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Not checked — no full text of the sourcecites [30] source
- Not checked — no full text of the sourcecites [121] source
- Supportedcites [40] source
Citation (40) is attached to the micropillars example. The paper reports fabricating micropost arrays and using them to study changes in cell morphology and stem-cell differentiation (Abstract; Online Methods, ‘Design and fabrication of PDMS micropost arrays’; page unavailable). (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 14
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“PDMS wells with a triangular pyramid shape opening promoted the growth of spheroids, with some control over the size achievable.”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Disputedcites [110] sourceExperimental — accuracy not yet measured
The Experimental section (‘Plate design, fabrication, and hanging drop formation’; page unavailable) says the plate is made of polystyrene, not PDMS, and describes circular access holes and plateaus by diameter, not triangular-pyramid openings. The Results section (‘Formation of hanging drops for spheroid culture’; page unavailable) does support spheroid formation, while the Introduction says the platform forms uniformly sized spheroids. The claimed well material and opening shape are contrary to the paper’s design description. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Disputed
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“To overcome this limitation, novel 3D cell culture platforms are being created to better mimic in vivo conditions and are sometimes called spheroid or organoid culture, as described below (37,61,84,98,117,118).”
§ 2D vs. 3D Cell Culture > Abstract
What the sources say
- Not checked — no full text of the sourcecites [37] source
- Could not verifycites [61] sourceExperimental — accuracy not yet measured
The Methods section describes cells plated on hydrogels, microposts, and adhesive micro-islands, while ‘Engineered microenvironments regulate LA/C-C epitope accessibility’ examines their effects on the nuclear lamina. Searches for spheroid or organoid culture and for 3D platforms that mimic in vivo conditions found no passage addressing the claim; the paper’s engineered substrates alone do not establish it. (LLM, conf=0.77)
- Not checked — no full text of the sourcecites [84] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“They demonstrated that cells preferred to round up on smooth-surfaced PLLA substrates and stretch on rough surfaces.”
§ 2D vs. 3D Cell Culture > Micro-pattering.
What the sources say
- Could not verifycites [113] sourceExperimental — accuracy not yet measured
The Materials and Methods section describes breast cells cultured in basement membrane, and the Abstract discusses integrin–EGFR signaling. Searches for PLLA, surface roughness, and rounded versus stretched cells found no passage addressing the claimed substrate comparison. (LLM, conf=0.75)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Torisawa et al. (110) created a novel chip system utilizing microfluidics that allows spheroids to grow in a controlled environment for long-term culture.”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Partly supportedcites [110] sourceExperimental — accuracy not yet measured
The Introduction and the Results and discussion section on long-term culture support that the authors developed a platform for stable, long-term spheroid culture. But the Experimental section describes their system as an injection-molded 384 hanging-drop plate, not a microfluidic chip; the Introduction discusses microfluidic devices as other approaches. Torisawa is a coauthor, although Tung is the paper’s first author. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Their results showed that the sandwich culture could maintain a proper albumin production rate for at least 6 wk, whereas the one-gel system already had rates that were tenfold lower than normal by the end of the first week (29).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results (p. 1045) say sandwich cultures maintained albumin production for at least six weeks and that production rates differed roughly tenfold between the sandwich and single-gel systems by the end of week one. The paper does not say the single-gel production rate was tenfold lower than normal; its comparison with normal liver concerns albumin mRNA levels, not production rates. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Cell growth in 2D monolayers allows for access to a similar amount of nutrients and growth factors present in the medium, which results in homogenous growth and proliferation (31).”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Supportedcites [31] source
The ‘Characteristics of 3D Cell Cultures Versus the Traditional 2D Cell Culture’ section says all cells in a 2D monolayer receive a homogeneous amount of nutrients and growth factors and that the monolayer is mainly composed of proliferating cells. Its contrast with the varied cell states in 3D cultures supports the paraphrase about homogeneous growth and proliferation. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“In 2D cultures, there are decreases in transcriptional genes and rapid changes in morphology (29,34).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results (p. 1047) show that albumin-gene transcription declined over seven days in hepatocytes cultured on a single collagen gel. The Discussion (p. 1050) mentions a change in actin-filament organization when hepatocytes are sandwiched between collagen gels, but does not establish rapid morphological changes in the single-gel culture. The claim also generalizes a finding about specific genes in rat hepatocytes to 2D cultures broadly. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [34] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“The effect of microtopography on cell migration was further supported by Wan et al. (113), whose experiments also revealed that pseudopods extending from cells could encroach into pits in culture surfaces.The less rigid pseudopods could act as anchors for the cell and influence its migration patterns, thereby providing a contact guidance (113).”
§ 2D vs. 3D Cell Culture > Micro-pattering.
What the sources say
- Could not verifycites [113] sourceExperimental — accuracy not yet measured
The Abstract describes β1-integrin and EGFR signaling in three-dimensional breast-cell cultures, not migration over patterned surfaces. Searches for pseudopods, pits, microtopography, anchors, and contact guidance found no passage addressing the attributed experiments. The cited paper is by Wang et al., whereas the citing sentence names Wan et al. (LLM, conf=0.75)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Surfaces of the aggregated spheroids, for example, have the highest levels of proliferation, whereas the interior of the 3D cell bodies possesses the highest number of quiescent or necrotic cells (31).”
§ 2D vs. 3D Cell Culture > Considerations
What the sources say
- Partly supportedcites [31] sourceExperimental — accuracy not yet measured
In “Characteristics of 3D Cell Cultures Versus the Traditional 2D Cell Culture” (page unavailable), the paper says spheroid outer layers are mainly proliferating and core cells tend to be quiescent or hypoxic. It lists necrotic cells among the cells in spheroids, but does not say they are concentrated in the interior or establish where the highest numbers occur. (LLM, conf=0.86)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“They continued on to use these plates as a high throughput method for testing anticancer drug sensitivities on H9 human epithelial carcinoma cells.”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Partly supportedcites [55] sourceExperimental — accuracy not yet measured
The Materials and Methods section (Hanging Drop Formation and Spheroid Culture; page unavailable) confirms that Hsiao et al. used 384 hanging-drop plates to culture cancer-containing spheroids. It describes PC-3Luc GFP prostate cancer cells in a co-culture, not H9 cells, and the experiment assessed long-term culture rather than anticancer drug sensitivity. (LLM, conf=0.87)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Biopolymers from non-mammal tissues, such as alginate and chitosan, are also used for making 3D scaffolds (23,63,68,84).”
§ 2D vs. 3D Cell Culture > Biopolymer scaffolds.
What the sources say
- Partly supportedcites [23] sourceExperimental — accuracy not yet measured
The Introduction describes alginate as a naturally derived polysaccharide, and the Conclusion reports using alginate hydrogels for in vitro 3D cell culture. This supports alginate as a 3D scaffold material, but the paper does not identify its source as non-mammalian or address chitosan. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [63] source
- Not checked — no full text of the sourcecites [68] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“To overcome this, one group, Hsiao et al. (55), designed a plate using micro-ring structures to stabilize the drops, allowing for 14day culture of prostate cancer cells.”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Supportedcites [55] source
The Introduction describes a modified hanging-drop plate with micro-ring features designed to stabilize droplets. Materials and Methods reports 14-day culture of spheroids containing PC-3Luc GFP prostate cancer cells, and Results and Discussion reports that the drops remained stable throughout that period. The cells were grown in co-culture, a detail the citing sentence omits but does not contradict. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Among the most commonly used natural polymers are hyaluronic acid, gelatin, collagen, and chondroitin sulfate (14, 108).”
§ 2D vs. 3D Cell Culture > Biopolymer scaffolds.
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) identifies hyaluronic acid and collagen as materials investigated for cartilage scaffolds, supporting their use as natural biomaterials. It does not identify gelatin as a commonly used material, and mentions chondroitin sulfate as a cartilage component rather than as a commonly used polymer. It also does not establish that the four named materials are among the most commonly used. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [108] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Pineda et al.(91) demonstrated that OCT4 in mouse ESCs decreased in both 2D and 3D cultures, showing a loss of pluripotency, whereas NES (ectoderm) and BRACHY-T (mesoderm) markers were shown to increase.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
What the sources say
- Partly supportedcites [91] sourceExperimental — accuracy not yet measured
In Results, ‘Pluripotency and Germ Lineage Differentiation’ (page unavailable), OCT4 markedly decreased after four days in the 2D slide and 3D gel and embryoid-body cultures, indicating loss of pluripotency. The same section says NESTIN (NES) and BRACHY-T varied over time and were highest at day 4, rather than showing a general increase; ‘Functional Gene Groupings’ also reports that NES remained very low. (LLM, conf=0.85)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Their results from 2D and 3D spheroid culture indicated spheroids were more resistant to one anti-cancer drug, 5-fluorouracil, which inhibits proliferation, whereas 2D cultures were more resistant to a different anticancer drug, tirapazamine, which is cytotoxic in hypoxic conditions (111).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Could not verifycites [111] sourceExperimental — accuracy not yet measured
The Introduction discusses stem-cell culture platforms and small-molecule screens, but does not report a 2D-versus-spheroid drug-response comparison. Searches for spheroids, 5-fluorouracil, and tirapazamine found no passage addressing the claimed resistance results; the indexed passages provide no page numbers. (LLM, conf=0.76)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
In the paper
“LeCluyse et al. (73) found that the polarity of hepatocytes was also affected when cultured on only single-layer gels.When a sandwich culture was used, a normal distribution of the apical membrane markers was found at the canalicular membrane, and bile canaliculi were also well established (73).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Not checked — no full text of the sourcecites [73] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The results indicated that the micro-patterning and type of surface both affected the rate of differentiation of cells (18).”
§ 2D vs. 3D Cell Culture > Micro-pattering.
What the sources say
- Not checked — no full text of the sourcecites [18] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Overall, 3D platforms are likely to provide an increasingly attractive alternative for 2D cell culture as the technology develops to enable a wider range of processes.”
§ 2D vs. 3D Cell Culture > Abstract
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: 2D cell culture approaches can still recapitulate in vivo behavior for many bioactivities.
In the paper
“Micropatterning can also be used to pattern areas or to create “microwells” for the controlled growth of spheroids (i.e., agarose) (35).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Not checked — no full text of the sourcecites [35] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“These methods allow for a more physiologically relevant environment to investigate cell and tissue behavior.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Three-dimensional studies are becoming increasingly necessary to replicate the behaviors of some in vivo conditions.
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
“different cell types will most likely be better matched for certain 3D systems.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“Additionally, microwells made out of a non-adhesion promoting material, such as agarose, can be used to grow several arrays of spheroids at once (86).”
§ 2D vs. 3D Cell Culture > Techniques
What the sources say
- Not checked — no full text of the sourcecites [86] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“In some cases, 2D studies are more feasible, and the results can be meaningful.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no 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
“In conclusion, the situation and questions at hand will determine whether a 2D or 3D culture method is best suited.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
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
“However, in other cases, 3D studies will yield more accurate results and can be done in combination with 2D studies.”
§ 2D vs. 3D Cell Culture > Conclusions and Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
Under some circumstances, 2D systems produce cell bioactivities that deviate appreciably from the in vivo response.
“Although these approaches are well-accepted and have significantly advanced our understanding of cell behavior, growing evidence now shows that, under some circumstances, the 2D systems can result in cell bioactivities that deviate appreciably the in vivo response.”
The paper relies on this without support.
2D cell culture approaches can still recapitulate in vivo behavior for many bioactivities.
“additionally, 2D cell culture approaches can still recapitulate in vivo behavior for many bioactivities, while new advances in substrate”
The paper relies on this without support.
A universal 3D platform does not currently exist.
“the platform of choice is often dictated by the specific process of interest, and a universal 3D platform does not currently exist”
The paper relies on this without support.
Most 2D methods do not provide control of cell shape.
“However, most of these 2D methods do not provide control of cell shape, which determines biophysical cues affecting cell bioactivities in vivo.”
The paper relies on this without support.
Hepatocytes do not survive well under traditional 2D culture methods.
“Indeed, alternative methods to traditional 2D cell culture were developed for hepatocytes because they do not survive well under traditional 2D culture methods.”
The paper relies on this without support.
A major problem in the field is the lack of a standard approach in three-dimensional cultures.
“One major problem in the field is the lack of a standard approach in 3D cultures”
The paper relies on this without support.
Two-dimensional cell culture practice is standard and roughly comparable.
“whereas 2D cell culture practice is standard and roughly comparable.”
The paper relies on this without support.
Three-dimensional studies are becoming increasingly necessary to replicate the behaviors of some in vivo conditions.
“Classically, 2D studies have been favored, but 3D studies are becoming more necessary to replicate the behaviors of some in vivo conditions.”
The paper relies on this without support.
Accurate measurements of the forces exerted on the extracellular matrix are necessary for understanding physiological processes such as cancer or immune cell migration.
“Obtaining accurate measurements of forces exerted on the ECM are necessary to understand physiological processes such as cancer or immune cell migration.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Cells grow on a fl at plastic surface as a monolayer, and this can result in loss of crucial cellular signaling pathways and changes in cell responses to stimuli [14 -16].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [14]
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
“Nevertheless, 2D models are too simple and are unable to mimic the complexity and dynamic interactions of the TME.”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [14]
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
“Generally, 2D cell culture models lack cues provided by the extracellular matrix (ECM). These models are easy to maintain and cost-effective but do not allow the study of glia-neuron communication and crosstalk [119].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [119]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“3D models can reproduce mechanical and biochemical cues that are crucial for cancer development, such as morphology, cell -cell/cell -ECM interactions, tissue stiffness, and speci fi c gradients [4,14,18].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [14]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The development of hepatocyte sandwich cultures (SCs), co-cultures with non-parenchymal cells and even more advanced 3-dimensional culturing techniques has revealed the importance of cell-cell and cell-matrix interactions for improving hepatic functions in liver models (Bachmann et al., 2015[2]; Duval et al., 2017[9]; Wei et al., 2018[45]).”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Duval et al., 2017[9]
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.
Diagnostic-tool claim cites a scaffold study
MinorReference 95 is identified as a study of bone-scaffold porosity and stem cells, rather than microfluidic diagnostic tools.
“as a diagnostic tool in developing countries (95)”
“95. Salerno A, Guarnieri D, Iannone M, Zeppetelli S, Netti PA. Effect of micro-and macroporosity of bone tissue three-dimensional-poly(epsilon-cap- rolactone) scaffold on human mesenchymal stem cells invasion, proliferation, and differentiation in vitro.”
Cancer-cell claim cites a paper on porous beads
MinorThe citation attached to the claim about cancer cells in 2D culture is listed as a paper on beads with controllable pore sizes.
“some important characteristics of cancer cells cannot be appropriately modeled in 2D cultures (22).”
“22. Choi SW, Yeh YC, Zhang Y, Sung HW, Xia Y. Uniform beads with controllable pore sizes for biomedical applications.”
PDMS claim cites a skin-grafting review
MinorThe cited reference 107 is identified as a paper on skin grafting and wound treatment, not PDMS behavior in cell-culture devices.
“PDMS does not corrode or become affected by aqueous solutions used in cell culture, pressure, or temperature, and cells are able to survive or grow as a result (107).”
“107. Sun BK, Siprashvili Z, Khavari PA. Advances in skin grafting and treatment of cutaneous wounds.”
Gas-foaming citation identifies a bioreactor study
MinorThe reference given for scaffold fabrication by gas foaming is listed as a study of embryonic stem-cell cardiogenesis using a liquid-marble micro-bioreactor.
“gas foaming (96)”
“96. Sarvi F, Jain K, Arbatan T, Verma PJ, Hourigan K, Thompson MC, Shen W, Chan PPY. Cardiogen- esis of embryonic stem cells with liquid marble micro-bioreactor.”
Citations
Cites
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915
The origins and the future of microfluidics
Whitesides, G. M. (2006) · Nature · doi:10.1038/nature05058 · Cited by 9,687
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Discher, D. E., Janmey, P., & Wang, Y.-L. (2005) · Science · doi:10.1126/science.1116995 · Cited by 6,382
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
Lutolf, M. P., & Hubbell, J. A. (2005) · Nature Biotechnology · doi:10.1038/nbt1055 · Cited by 4,551
Reconstituting organ-level lung functions on a chip
Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E. (2010) · Science · doi:10.1126/science.1188302 · Cited by 4,250
Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment
McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K., & Chen, C. S. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00075-9 · Cited by 4,182
Porous scaffold design for tissue engineering
Hollister, S. J. (2005) · Nature Materials · doi:10.1038/nmat1421 · Cited by 3,979
Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305
Taking Cell-Matrix Adhesions to the Third Dimension
Cukierman, E., Pankov, R., Stevens, D. R., & Yamada, K. M. (2001) · Science · doi:10.1126/science.1064829 · Cited by 3,027
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of 3D cell migration
Yamada, K. M., & Sixt, M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0172-9 · Cited by 906
Wound healing, fibroblast heterogeneity, and fibrosis
desJardins-Park, H. E., Mascharak, S., Griffin, M., Wan, D. C., & Longaker, M. T. (2022) · Cell stem cell · doi:10.1016/j.stem.2022.07.006 · Cited by 835
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
“These models are easy to maintain and cost-effective but do not allow the study of glia-neuron communication and crosstalk [119].”
Background3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions
Rodrigues, J., Heinrich, M. A., Teixeira, L. M., & Prakash, J. (2021) · Trends in Cancer · doi:10.1016/j.trecan.2020.10.009 · Cited by 405
“Cell interactions Deprived of cell–cell and cell–ECM interactions, no cell niches are created Cell junctions are common and allow cell communication [14]”
BackgroundConductive biomaterials for muscle tissue engineering
Dong, R., Ma, P. X., & Guo, B. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119584 · Cited by 387
Tumor microenvironment: barrier or opportunity towards effective cancer therapy
Tiwari, A., Trivedi, R., & Lin, S. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00866-3 · Cited by 399
“However, the cells in 2D co-cultures form a monolayer, and thus the models are unable to accurately mimic the TME’s complex cellular interactions and signaling pathways [30, 184, 185].”
BackgroundCollagen in tendon, ligament, and bone healing. A current review.
Liu, S. H., Yang, R. S., Al-Shaikh, R. A., & Lane, J. M. (1995) · PubMed · Cited by 323
Boularaoui, S. M., Hussein, G. A., Khan, K. A., Christoforou, N., & Stefanini, C. (2020) · Bioprinting · doi:10.1016/j.bprint.2020.e00093 · Cited by 349
3D‐Bioprinted Mini‐Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics
Heinrich, M. A., Bansal, R., Lammers, T., Zhang, Y. S., Schiffelers, R. M., & Prakash, J. (2019) · Advanced Materials · doi:10.1002/adma.201806590 · Cited by 327
Costa, L. A., Eiró, N., Fraile, M., González, L. O., Saá, J., García-Portabella, P., Vega, B., Schneider, J., & Vizoso, F. J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03600-0 · Cited by 328
Desai, N., Rana, D., Patel, M., Bajwa, N., Prasad, R., & Vora, L. K. (2025) · Small · doi:10.1002/smll.202502315 · Cited by 341
Tang, M., Xie, Q., Gimple, R. C., Zhong, Z., Tam, T., Tian, J., Kidwell, R. L., Wu, Q., Prager, B. C., Qiu, Z., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0338-1 · Cited by 311
“Further development of tissue engineering approaches informs new 3D culture systems with improved scalability and capacity to tune specific biological parameters, including cellular composition and extracellular matrix stiffness.(19) The development of physiologically relevant brain tumor microenvironments(20) require…”
BackgroundThe function and mechanism of ferroptosis in cancer
Wang, Y., Wei, Z., Pan, K., Li, J., & Chen, Q. (2020) · APOPTOSIS · doi:10.1007/s10495-020-01638-w · Cited by 262
3D cell culture stimulates the secretion of in vivo like extracellular vesicles
Thippabhotla, S., Zhong, C., & He, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-49671-3 · Cited by 268
Ahmed, R. E., Anzai, T., Chanthra, N., & Uosaki, H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00178 · Cited by 258
Engineering Multi‐Cellular Spheroids for Tissue Engineering and Regenerative Medicine
Kim, S., Kim, E. M., Yamamoto, M., Park, H., & Shin, H. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000608 · Cited by 241
Gut-on-a-chip: Current progress and future opportunities
Ashammakhi, N. A., Nasiri, R., de Barros, N. R., Tebon, P. J., Thakor, J., Goudie, M. J., Shamloo, A., Martín, M. G., & Khademhosseini, A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120196 · Cited by 255
Shin, H., Jeong, S., Lee, J., Sun, W., Choi, N., & Cho, I. (2021) · Nature Communications · doi:10.1038/s41467-020-20763-3 · Cited by 227
Strategies to use fibrinogen as bioink for 3D bioprinting fibrin-based soft and hard tissues
de Melo, B. A. G., Jodat, Y. A., Cruz, E. M., Benincasa, J. C., Shin, S. R., & Porcionatto, M. A. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.09.024 · Cited by 229
Breast cancer models: Engineering the tumor microenvironment
Bahcecioglu, G., Basara, G., Ellis, B. W., Ren, X., & Zorlutuna, P. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.02.006 · Cited by 213
Kim, W., Gwon, Y., Park, S., Kim, H., & Kim, J. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.039 · Cited by 216
Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application
Ceccarelli, S., Pontecorvi, P., Anastasiadou, E., Claudio Napoli, A., & Marchese, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00236 · Cited by 219
Borciani, G., Montalbano, G., Baldini, N., Cerqueni, G., Vitale‐Brovarone, C., & Ciapetti, G. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.03.043 · Cited by 209
“In addition, even if the 2D culture system is attractive to biologists for its simplicity and efficiency, most of the 2D models do not provide control of the cell shape, which in turn influences cell activities [103 , 104] .”
BackgroundHydrogel systems and their role in neural tissue engineering
Madhusudanan, P., Raju, G., & Shankarappa, S. A. (2020) · Journal of The Royal Society Interface · doi:10.1098/rsif.2019.0505 · Cited by 201
“Cytoskeletal forces that govern the movement of neurites in a 2D system are drastically different from the forces experienced in a 3D culture system that leads to neuronal migration and maturation [39].”
BackgroundRajan, S. A. P., Aleman, J., Wan, M., Zarandi, N. P., Nzou, G., Murphy, S. V., Bishop, C. E., Sadri‐Ardekani, H., Shupe, T., Atala, A., et al. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.02.015 · Cited by 210
Microfluidics for Drug Development: From Synthesis to Evaluation
Liu, Y., Sun, L., Zhang, H., Shang, L., & Zhao, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01289 · Cited by 211
Nassar, Z. D., Mah, C. Y., Dehairs, J., Burvenich, I. J. G., Irani, S., Centenera, M. M., Helm, M., Shrestha, R. K., Moldovan, M. V., Don, A. S., et al. (2020) · eLife · doi:10.7554/elife.54166 · Cited by 199
“DECR1 knockdown also decreased LNCaP growth in 3D spheroids (Figure 5F), which better mimic in vivo conditions than 2dimensional cell culture (Duval et al., 2017).”
BackgroundAdvances in the Biofabrication of 3D Skin in vitro: Healthy and Pathological Models
Randall, M. J., Jüngel, A., Rimann, M., & Wuertz‐Kozak, K. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00154 · Cited by 202
“Although these 2D cell culture systems have played a key role in furthering our understanding of molecular signaling, cellular morphology, and drug discovery, not all results and conclusions from these 2D cell culture systems are translatable to physiological in vivo systems (Duval et al., 2017; Langhans, 2018).”
Background3D bioprinting for cardiovascular regeneration and pharmacology
Cui, H., Miao, S., Esworthy, T. J., Zhou, X., Lee, S., Liu, C., Yu, Z., Fisher, J. P., Mohiuddin, M. M., & Zhang, L. G. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.07.014 · Cited by 200
Candini, O., Grisendi, G., Foppiani, E. M., Brogli, M., Aramini, B., Masciale, V., Spano, C., Petrachi, T., Veronesi, E., Conte, P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-43613-9 · Cited by 200
Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells
Ho, B. X., Pek, N. M. Q., & Soh, B.-S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040936 · Cited by 185
“Many recent studies have shown that the attributions of the surfaces that cells grow on in 2D models influence the cellular and molecular characteristics of the cells, such as cell development, proliferation, differentiation, apoptosis, and cell migratory behaviors [52].”
BackgroundModels of Osteoarthritis: Relevance and New Insights
Samvelyan, H. J., Hughes, D., Stevens, C., & Staines, K. A. (2020) · Calcified Tissue International · doi:10.1007/s00223-020-00670-x · Cited by 195
Advances in Engineering Human Tissue Models
Moysidou, C., Barberio, C., & Owens, R. M. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.620962 · Cited by 193
“These inherent limitations and shortcomings of 2D cell systems ultimately lead to failures in understanding cell behavior in healthy or diseased states (Duval et al., 2017).”
BackgroundTao, T., Deng, P., Wang, Y., Zhang, X., Guo, Y., Chen, W., & Qin, J. (2022) · Advanced Science · doi:10.1002/advs.202103495 · Cited by 178
Optimization of cell-laden bioinks for 3D bioprinting and efficient infection with influenza A virus
Berg, J., Hiller, T., Kissner, M. S., Qazi, T. H., Duda, G. N., Hocke, A. C., Hippenstiel, S., Elomaa, L., Weinhart, M., Fahrenson, C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31880-x · Cited by 180
Cardoso, B. D., Castanheira, E. M. S., Lanceros-Méndez, S., & Cardoso, V. F. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202202936 · Cited by 171
Krenn, V., Bosone, C., Burkard, T. R., Spanier, J., Kalinke, U., Calistri, A., Salata, C., Christoff, R. R., Garcez, P. P., Mirazimi, A., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.03.004 · Cited by 161
Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling
Akbari, S., Sevinç, G. G., Ersoy, N., Başak, O., Kaplan, K. N., Sevinç, K., Ozel, E., Şengün, B., Enüstün, E., Özçimen, B., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.08.007 · Cited by 158
Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing
Bédard, P., Gauvin, S., Ferland, K., Caneparo, C., Pellerin, È., Chabaud, S., & Bolduc, S. (2020) · Bioengineering · doi:10.3390/bioengineering7030115 · Cited by 167
“Since cell behaviour, like cell differentiation, migration, morphogenesis, and proliferation, has been proven to be highly influenced by its biochemical and biomechanical microenvironments [47], 2D cell culture can lead to results that deviate from in vivo responses [52,53].”
BackgroundMicrofluidic Formulation of Topological Hydrogels for Microtissue Engineering
Rojek, K. O., Ćwiklińska, M., Kuczak, J., & Guzowski, J. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00798 · Cited by 153
Current Strategies to Enhance Adipose Stem Cell Function: An Update
Seo, Y., Shin, T., & Kim, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153827 · Cited by 149
“Until now, the spheroid method was widely applied to culture neural stem cells (neurosphere), embryonic stem cells (embryonic body), cancer cells (tumoroid), and other cells to study developmental and physiopathological cell-to-cell dynamics in vitro [144,147].”
BackgroundMethodInfluentialRinoldi, C., Costantini, M., Kijeńska‐Gawrońska, E., Testa, S., Fornetti, E., Heljak, M. K., Ćwiklińska, M., Buda, R., Baldi, J., Cannata, S. M., et al. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801218 · Cited by 146
Heterogeneous microenvironmental stiffness regulates pro-metastatic functions of breast cancer cells
Liu, C., Li, M., Dong, Z.-X., Jiang, D., Li, X., Lin, S., Chen, D., Zou, X., Zhang, X., & Luker, G. D. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.07.009 · Cited by 143
3D Cell Cultures: Evolution of an Ancient Tool for New Applications
Cacciamali, A., Villa, R., & Dotti, S. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.836480 · Cited by 166
“As described in several papers (Antoni et al., 2015; Duval et al., 2017; Terrel et al., 2020), it should consider different aspects in order to choose the better in vitro model to use.”
BackgroundMethodInfluentialCells grown in three-dimensional spheroids mirror in vivo metabolic response of epithelial cells
Lagies, S., Schlimpert, M., Neumann, S., Waeldin, A., Kammerer, B., Borner, C., & Peintner, L. (2020) · Communications Biology · doi:10.1038/s42003-020-0973-6 · Cited by 132
Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin
Sutterby, E., Thurgood, P., Baratchi, S., Khoshmanesh, K., & Pirogova, E. (2020) · Small · doi:10.1002/smll.202002515 · Cited by 142
Dynamic Covalent Hydrogels: Strong yet Dynamic
Han, Y., Cao, Y., & Lei, H. (2022) · Gels · doi:10.3390/gels8090577 · Cited by 158
Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition
Lad, H., Saumur, T. M., Herridge, M. S., dos Santos, C. C., Mathur, S., Batt, J. A. E., & Gilbert, P. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217840 · Cited by 150
“Although differentiating human myogenic progenitors into multinucleated myotubes is straightforward in 2D culture, the cultures fail to mimic the natural tissue structure of adult human skeletal muscle tissue and lack the cell–cell and cell–extracellular environment interactions that exist in vivo [212,213].”
BackgroundOrganic Bioelectronics for In Vitro Systems
Pitsalidis, C., Pappa, A., Boys, A. J., Fu, Y., Moysidou, C., van Niekerk, D. C., Sáez, J., Savva, A., Iandolo, D., & Owens, R. M. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00539 · Cited by 141
Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells
Cuenca, M. V., Cochrane, A., van den Hil, F. E., de Vries, A. A. F., Oberstein, S. A. J. L., Mummery, C. L., & Orlova, V. V. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.08.003 · Cited by 140
Wang, J., Li, B., Luo, M., Huang, J., Zhang, K., Zheng, S., Zhang, S., & Zhou, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01779-3 · Cited by 157
“205 However, it fails to re fl ect the natural construction of the tumor which reduces the potential to translate results into 3D, in vivo models, and clinical practice.”
BackgroundPamies, D. (2018) · ALTEX · doi:10.14573/altex.1710081 · Cited by 127
Design and Fabrication of Organ-on-Chips: Promises and Challenges
Tajeddin, A., & Mustafaoğlu, N. (2021) · Micromachines · doi:10.3390/mi12121443 · Cited by 143
“This shape enhancement helps improve cell function in vitro, which has led researchers to incorporate more advanced environments into cell culture systems to create 3D models and develop techniques, such as sandwich culturing, microstructuring, and substrate stiffness modification [7].”
BackgroundAdvanced Strategies for 3D Bioprinting of Tissue and Organ Analogs Using Alginate Hydrogel Bioinks
Gao, Q., Kim, B.-S., & Gao, G. (2021) · Marine Drugs · doi:10.3390/md19120708 · Cited by 134
“The cellular function is commonly mediated by the structural and compositional cues provided by the given microenvironment, such as micro-topological structure, mechanical strength, critical molecule presence, and growth factor gradients [55].”
BackgroundReview of 3D cell culture with analysis in microfluidic systems
Castiaux, A. D., Spence, D. M., & Martin, R. S. (2019) · Analytical Methods · doi:10.1039/c9ay01328h · Cited by 134
Logan, S., Arzua, T., Canfield, S. G., Seminary, E. R., Sison, S. L., Ebert, A. D., & Bai, X. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180025 · Cited by 143
“The likelihood of reproducibility through differentiation batches is higher, and it is easier to analyze the types of cells present, and cell type-specific physiology (134).”
Extracellular matrix dynamics in cell migration, invasion and tissue morphogenesis
Yamada, K. M., Collins, J. W., Walma, D. A. C., Doyle, A. D., Morales, S. R. G., Lu, J., Matsumoto, K., Nazari, S., Sekiguchi, R., Shinsato, Y., et al. (2019) · International Journal of Experimental Pathology · doi:10.1111/iep.12329 · Cited by 124
Evaluating CAR‐T Cell Therapy in a Hypoxic 3D Tumor Model
Ando, Y., Siegler, E. L., Ta, H. P., Cinay, G. E., Zhou, H., Gorrell, K. A., Au, H., Jarvis, B. M., Wang, P., & Shen, K. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201900001 · Cited by 115
Jeong, M., Ocwieja, K. E., Han, D., Wackym, P. A., Zhang, Y., Brown, A., Moncada-Reid, C., Vambutas, A., Kanne, T. J., Crain, R., et al. (2021) · Communications Medicine · doi:10.1038/s43856-021-00044-w · Cited by 116
A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
Yankaskas, C. L., Thompson, K. N., Paul, C. D., Vitolo, M. I., Mistriotis, P., Mahendra, A., Bajpai, V. K., Shea, D. J., Manto, K. M., Chai, A. C., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0400-9 · Cited by 113
The role of MET in chemotherapy resistance
Wood, G. E., Hockings, H., Hilton, D. M., & Kermorgant, S. (2021) · Oncogene · doi:10.1038/s41388-020-01577-5 · Cited by 113
“In addition, many important characteristics of cancer cells cannot be appropriately modelled in 2D cultures, including exposure to growth factors, cellular polarity and cellular adhesion [89, 90].”
Background3D Bioprinting of Tumor Models for Cancer Research
Kang, Y., Datta, P., Shanmughapriya, S., & Ozbolat, I. T. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00791 · Cited by 112
Cancer Modeling‐on‐a‐Chip with Future Artificial Intelligence Integration
Fetah, K., DiPardo, B. J., Kongadzem, E.-M. L., Tomlinson, J. S., Elzagheid, A. I., Elmusrati, M. S., Khademhosseini, A., & Ashammakhi, N. A. (2019) · Small · doi:10.1002/smll.201901985 · Cited by 116
Bioengineering Approaches for Corneal Regenerative Medicine
Mahdavi, S. S., Abdekhodaie, M. J., Mashayekhan, S., Baradaran‐Rafii, A., & Djalilian, A. R. (2020) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-020-00262-8 · Cited by 112
Liver Microphysiological Systems for Predicting and Evaluating Drug Effects
Ribeiro, A. J. S., Yang, X., Patel, V. P., Madabushi, R., & Strauss, D. G. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1458 · Cited by 114
“In general, 3D microenvironments and co cultures of tissue- specific cells mimic organ physiology better than monocultures of cells in traditional two- dimensional (2D) plates/dishes.(7) In accordance with this definition of MPS, the achievements, potential, and challenges of using hepatic/liver MPS in drug developmen…”
BackgroundEndometriosis: current challenges in modeling a multifactorial disease of unknown etiology
Malvezzi, H., Marengo, E. B., Podgaec, S., & Piccinato, C. D. A. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02471-0 · Cited by 117
Chen, S., Wang, H., Mainardi, V. L., Talò, G., McCarthy, A. D., John, J. V., Teusink, M. J., Hong, L., & Xie, J. (2021) · Science Advances · doi:10.1126/sciadv.abg3089 · Cited by 110
Optical clearing methods: An overview of the techniques used for the imaging of 3D spheroids
Costa, E. C., Silva, D., Moreira, A. F., & Correia, I. J. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.27105 · Cited by 115
Liver organoid as a 3D in vitro model for drug validation and toxicity assessment
Brooks, A., Liang, X., Zhang, Y., Zhao, C., Roberts, M. S., Wang, H., Zhang, L., & Crawford, D. H. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105608 · Cited by 111
Dabbagh, S. R., Sarabi, M. R., Birtek, M. T., Mustafaoğlu, N., Zhang, Y. S., & Taşoğlu, S. (2022) · Aggregate · doi:10.1002/agt2.197 · Cited by 114
Liver organ-on-chip models for toxicity studies and risk assessment
Messelmani, T., Morisseau, L., Sakai, Y., Legallais, C., Goff, A. L., Leclerc, É., & Jellali, R. (2022) · Lab on a Chip · doi:10.1039/d2lc00307d · Cited by 113
Polymer Hydrogels to Guide Organotypic and Organoid Cultures
Magno, V., Meinhardt, A., & Werner, C. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202000097 · Cited by 110
Organ-on-a-chip platforms for accelerating the evaluation of nanomedicine
Chen, X., Zhang, Y. S., Zhang, X., & Liu, C. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.09.022 · Cited by 112
Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies
Law, A. M. K., de la Fuente, L. R., Grundy, T. J., Fang, G., Valdés‐Mora, F., & Gallego‐Ortega, D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.782766 · Cited by 108
Fabrication techniques of biomimetic scaffolds in three‐dimensional cell culture: A review
Badekila, A. K., Kini, S., & Jaiswal, A. K. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29935 · Cited by 108
Droplet microfluidics-based biomedical microcarriers
Shao, C., Chi, J., Shang, L., Fan, Q., & Ye, F. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.10.037 · Cited by 106
Unravelling cell migration: defining movement from the cell surface
Merino-Casallo, F., Gómez‐Benito, M. J., Hervás-Raluy, S., & García‐Aznar, J. M. (2022) · Cell Adhesion & Migration · doi:10.1080/19336918.2022.2055520 · Cited by 123
Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models
Hermida, M. A., Kumar, J. D., Schwarz, D., Laverty, K. G., Bartolo, A. D., Ardron, M., Bogomolnijs, M., Clavreul, A., Brennan, P. M., Wiegand, U. K., et al. (2019) · Advances in Biological Regulation · doi:10.1016/j.jbior.2019.100658 · Cited by 106
“Extensive reviews have recently addressed the different approaches to the 3D culture of human cells without an adhesive substrate (Alhaque et al., 2018; Duval et al., 2017).”
BackgroundVainieri, M. L., Lolli, A., Kops, N., et al. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.11.015 · Cited by 105
Stretchable Electrochemical Sensors for Cell and Tissue Detection
Liu, Y., & Huang, W. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202007754 · Cited by 105
In vitro 3d cultures to model the tumor microenvironment
Fontana, F., Marzagalli, M., Sommariva, M., Gagliano, N., & Limonta, P. (2021) · Cancers · doi:10.3390/cancers13122970 · Cited by 103
“Although 2D systems have provided an invaluable tool to investigate the molecular bases of tumor biology and promote the preclinical development of many anti-cancer drugs over the years, the limits of this technology are evident [13,14].”
BackgroundRecent advances in lung-on-a-chip models
Francis, I., Shrestha, J., Paudel, K. R., Hansbro, P. M., Warkiani, M. E., & Saha, S. C. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.06.004 · Cited by 118
Guidance document on Good cell and tissue culture practice 2.0 (GCCP 2.0)
Pamies, D. (2021) · ALTEX · doi:10.14573/altex.2111011 · Cited by 100
“…such as the deposition of extracellular matrix, secretion of growth factors, altered cell proliferation, morphological development, lineage differentiation, changes in gene expression levels (Mabry et al., 2016), rate of cell death (Bonnier et al., 2015), or cell migration (Duval et al., 2017).”
BackgroundOlgasi, C., Cucci, A., & Follenzi, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176215 · Cited by 100
“This led to the development of three-dimensional (3D) cultures with high cell-extracellular matrix (ECM) and cell-cell interactions [11,12].”
BackgroundThe emergence of 3D bioprinting in organ-on-chip systems
Fetah, K., Tebon, P. J., Goudie, M. J., Eichenbaum, J., Ren, L. M., de Barros, N. R., Nasiri, R., Ahadian, S., Ashammakhi, N. A., Dokmeci, M. R., et al. (2019) · Progress in Biomedical Engineering · doi:10.1088/2516-1091/ab23df · Cited by 106
Tien, N.-D., Lyngstadaas, S. P., Mano, J. F., Blaker, J. J., & Haugen, H. J. (2021) · Molecules · doi:10.3390/molecules26092683 · Cited by 99
“Acting as a barrier to growth and migration, this can cause skin cells to behave abnormally and cause aberrant skin healing with fibrosis and scarring [123].”
BackgroundZhang, X., Wang, C., Liao, M., Dai, L., Tang, Y., Zhang, H., Coates, P. D., Sefat, F., Zheng, L., Song, J., et al. (2019) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2019.02.038 · Cited by 99
Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production
Djisalov, M., Knežić, T., Podunavac, I., Živojević, K., Radonić, V., Knežević, N. Ž., Bobrinetskiy, I. I., & Gadjanski, I. (2021) · Biology · doi:10.3390/biology10030204 · Cited by 102
“These cultures allow cells to grow in multiple directions, which is a step-up from the planar surface of the 2D cell cultures [99].”
BackgroundSpheroid Engineering in Microfluidic Devices
Tevlek, A., Keçili, S., Ozcelik, O. S., Külah, H., & Tekin, H. C. (2023) · ACS Omega · doi:10.1021/acsomega.2c06052 · Cited by 98
Grimaudo, M. A., Krishnakumar, G. S., Giusto, E., Furlani, F., Bassi, G., Rossi, A., Molinari, F., Lista, F. R., Montesi, M., & Panseri, S. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.11.038 · Cited by 98
Microenvironmental sensing by fibroblasts controls macrophage population size
Zhou, X., Franklin, R. A., Adler, M., Carter, T. S., Condiff, E., Adams, T. S., Pope, S. D., Philip, N. H., Meizlish, M. L., Kaminski, N., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2205360119 · Cited by 99
“Space limitation in vitro in tissue culture dishes is distinct from space limitation within tissues due to the complexity of tissue microenvironment (34).”
BackgroundEvolution of the Experimental Models of Cholangiocarcinoma
Massa, A., Varamo, C., Vita, F., Tavolari, S., Neia, C. P., Brandi, G., Rizzo, A., Cavalloni, G., & Aglietta, M. (2020) · Cancers · doi:10.3390/cancers12082308 · Cited by 96
Advancing 3D bioprinting through machine learning and artificial intelligence
Ramesh, S., Deep, A., Tamayol, A., Kamaraj, A. B., Mahajan, C., & Madihally, S. V. (2024) · Bioprinting · doi:10.1016/j.bprint.2024.e00331 · Cited by 99
Synthetic scaffolds for 3D cell cultures and organoids: applications in regenerative medicine
Marchini, A., & Gelain, F. (2022) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2021.1932716 · Cited by 91
Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis
Qiao, H., & Tang, T. (2018) · Bone Research · doi:10.1038/s41413-018-0008-9 · Cited by 94
“between metastatic cancer cells and neighbouring matrices.(32) Moreover, 3D systems promote rich cell–cell and cell–ECM interactions, which helps in the precise recapitulation of cancer bone metastasis at the tissue, cellular and molecular levels.”
BackgroundDecellularized tissues as platforms for in vitro modeling of healthy and diseased tissues
McCrary, M. W., Bousalis, D., Mobini, S., Song, Y. H., & Schmidt, C. E. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.05.031 · Cited by 98
Ramasamy, S., Davoodi, P., Vijayavenkataraman, S., Teoh, J. H., Thamizhchelvan, A. M., Robinson, K. S., Wu, B., Fuh, J. Y. H., DiColandrea, T., Zhao, H., et al. (2021) · Bioprinting · doi:10.1016/j.bprint.2020.e00123 · Cited by 96
3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives
Xiang, Y., Miller, K. L., Guan, J., Kiratitanaporn, W., Tang, M., & Chen, S. (2022) · Archives of Toxicology · doi:10.1007/s00204-021-03212-y · Cited by 100
Routine Optical Clearing of 3D-Cell Cultures: Simplicity Forward
Nürnberg, E., Vitacolonna, M., Klicks, J., von Molitor, E., Cesetti, T., Keller, F., Bruch, R., Ertongur-Fauth, T., Riedel, K., Scholz, P., et al. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00020 · Cited by 93
“The absence of nutrient and oxygen gradients, as well as restricted migration potential grown on a plastic surface, further contribute to a limited representation of physiology in 2D in vitro systems (Duval et al., 2017).”
BackgroundTechnical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models
Pavlacký, J., & Polak, J. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00057 · Cited by 99
“Introducing the element of three-dimensionality to cell cultures, which is arguably an intrinsic feature of all multicellular organisms, can improve the potential of in vitro models to recapitulate the in vivo environment (144).”
Background
Metadata
- Authors
- Duval, K., Grover, H., Han, L.-H., Mou, Y., Pegoraro, A. F., Fredberg, J., & Chen, Z.
- Affiliations
- Dartmouth College (US)
- Drexel University (US)
- University of Illinois Chicago (US)
- Harvard University (US)
- Corresponding author
- Chen, Zi
- Venue
- Physiology
- Publisher
- American Physiological Society
- Published
- 2017-07
- Volume
- 32
- Issue
- 4
- Pages
- 266-277
- ISSN
- 0886-1714 (ISSN-L)
- 1548-9213
- 1548-9221
- PMC
- PMC5545611
- OpenAlex
- W2626725994
- Cited by
- 1,849
- References
- 129
- Citations by year
- 2026: 184 · 2025: 240 · 2024: 251 · 2023: 252 · 2022: 241 · 2021: 268 · 2020: 234 · 2019: 127 · 2018: 46 · 2017: 4
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Physiology (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Society in Science-Branco Weiss Fellowship
- HHS | NIH | National Cancer Institute (NCI) (U01CA202123)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- 2D cell culture, 3D cell culture, tissue engineering, regenerative medicine, mechanical microenvironment, metabolic waste, physiological modeling, biomechanics
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Extracellular Matrix, Humans, Cell Culture Techniques, Tissue Engineering, Biomedical Research, Cell Proliferation
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 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (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 ›
Are you an author, or do you see a problem with this page? Request a review
