The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index; 2 of the 47 sources its claims cite were checked for support.
Physical vitrification and nanowarming at liter-scale CPA volumes: toward organ cryopreservation
Open accessPublished version of a preprint
Abstract
Organ banking via vitrification could transform transplantation, but has never been achieved at human organ scales. This study tested vitrification and rewarming in 0.5–3 L volumes using cryoprotective agents (CPAs): M22, VS55, and 40%EG + 0.6 M Sucrose. Ice formation and cracking was avoided through optimized convective cooling, and successful vitrification was confirmed via visual inspection, thermometry, and X-ray µCT. M22 and EG+sucrose vitrified at 0.5 L, but only M22 succeeded at 3 L; VS55 failed at all volumes. Porcine livers (~0.6–1 L total volume; ~0.23–0.75 L organ volume) were also vitrified using EG+sucrose, though not rewarmed. Future experiments are needed to optimize the protocol and achieve liver rewarming. Using nanowarming with iron-oxide nanoparticles and a newly developed 120 kW RF coil, uniform rewarming was achieved in up to 2 L volumes of M22 at ~88 °C/min. This work serves as a proof-of-concept that human organ scale vitrification and rewarming is physically possible, thereby enabling human organ banking in the future.
Overview
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Written from the paper’s full text.
TL;DR
This study demonstrates physical vitrification of cryoprotective agent volumes up to 3 L and uniform nanowarming up to 2 L, plus vitrification of porcine livers, as a proof-of-concept for human organ cryopreservation. M22 vitrified at all tested volumes, EG+sucrose up to 1 L, VS55 failed, and nanowarming achieved ~88 °C/min in 2 L.
Key findings
- M22 vitrified successfully at 0.5, 1, and 3 L; 40%EG + 0.6 M sucrose vitrified up to 1 L; VS55 failed at all volumes, with achieved center cooling rates of ~1.4, ~1, and ~0.5 °C/min for 0.5, 1, and 3 L, respectively, below VS55’s ~2.5 °C/min critical cooling rate.
- Porcine livers (~0.6–1 L total volume; ~0.23–0.75 L organ volume) perfused with 40%EG + 0.6 M sucrose were vitrified, with only small ice around the portal vein and fatty perihilar tissue; they were not rewarmed.
- A 120 kW RF coil generated up to 35 kA/m at 360 kHz, uniform within 5% over a 20 cm axial and 6 cm radial region; 1 L and 2 L M22 volumes nanowarmed at ~172 °C/min and ~88 °C/min, respectively, with temperature differences <5 °C.
- A 1 mL VMP sample with 100 mgFe/mL EMG308 reached ~1500 °C/min, reported as the fastest measured nanowarming rate; SAR increased ~1.5-fold at cryogenic versus room temperature.
Methods
- Heat transfer was modeled in COMSOL 5.4 for 0.5, 1, and 3 L cryobags, then vitrification used controlled-rate freezer protocols with verification by visual inspection, fiber optic thermometry, and µCT.
- Porcine livers (n = 5) from male Yorkshire pigs (9–30 kg) were perfused via the portal vein with 40%EG + 0.6 M sucrose using a step-loading protocol and vitrified in cryobags.
- Nanowarming used M22 with iron-oxide nanoparticles in cryobags inside a custom 120 kW RF coil, with fiber optic temperature probes; SAR was measured by the time-rise method, and experiments had ≥3 replicates.
Limitations
- Stated: no biological or functional assessment of organs was performed; no vitrified liver was nanowarmed because of the 120 kW RF coil diameter; perfusion protocols need optimization to minimize CPA toxicity and improve consistency.
- Stated: the study assumed full CPA equilibration in tissue, but organ perfusion often equilibrates only to ~92–94%; long-term storage effects, physical aging, devitrification, and optimal storage conditions require further study.
- Evident from the text: this is a physical proof-of-concept only, with no transplantation, viability, or toxicity outcomes; liver rewarming and human liver-scale (≥3 L) organ rewarming remain undemonstrated.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
2 of 47 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured
- Interpretationreasoning
The IONP required for a single human kidney is ~0.8-1.6 gFe when the estimated amount is multiplied by ~2-4 times the vascular volume to ensure complete perfusion loading.
“This amount should be multiplied by ~2 to 4 times the vascular volume to ensure complete perfusion loading14,15, elevating the IONP required for a single kidney to ~0.8–1.6 gFe.”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [14] Sharma, A. et al. Vitrification and Nanowarming of Kidneys. Adv. Sci. 8, 2101691 (2021). source
- cites [15] Han, Z. et al. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nat. Commun. 14, 3407 (2023). source
The Methods section, “Loading of nanoparticles” (page unavailable), describes perfusing IONPs into rat kidneys at 10 mg Fe/mL for 4–5 minutes. It does not give a 2–4-times-vascular-volume loading rule or estimate 0.8–1.6 gFe for a human kidney, so the quantitative extrapolation is not supported by this source. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation
Nanowarming of volumes up to 80 mL CPA and 30 mL biological at rates up to 50-100 °C/min has been published.
“So far, we and others have published on nanowarming of volumes up to 80 mL CPA mL and 30 mL biological nanowarming at rates up to 50–100 °C/min14–19 (see Table S1).”
Quote in the paperSubstantial claim1 of 6 sources checked- cites [14] Sharma, A. et al. Vitrification and Nanowarming of Kidneys. Adv. Sci. 8, 2101691 (2021). source
- cites [15] Han, Z. et al. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nat. Commun. 14, 3407 (2023). source
The Results section, “Kidney nanowarming and post-nanowarming assessment” (page not supplied), reports nanowarming a rat kidney at 72.0 ± 8.0 °C/min, within the claimed rate range. The Methods section, “Nanowarming of kidneys” (page not supplied), describes an approximately 80 mL coil bore, not 80 mL of CPA; our copy does not establish a 30 mL biological sample either. Thus this paper supports the nanowarming rate and biological-organ example, but not the claimed volumes. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [16] Zhan, T. et al. Fe3O4 nanoparticles with carboxylic acid functionality for improving the structural integrity of whole vitrified rat kidneys. ACS Appl. Nano Mater. 4, 13552–13561 (2021). source
- cites [17] Gao, Z. et al. Vitrification and rewarming of magnetic nanoparticle-loaded rat hearts. Adv. Mater. Technol. 7, 2100873 (2022). source
- cites [18] Chiu-Lam, A. et al. Perfusion, cryopreservation, and nanowarming of whole hearts using colloidally stable magnetic cryopreservation agent solutions. Sci. Adv. 7, eabe3005 (2021). source
- cites [19] Sharma, A. et al. Cryopreservation of whole rat livers by vitrification and nanowarming. Ann. Biomed. Eng. 51, 566–577 (2023). source
- Findingown data
SARV increased at cryogenic temperature by ~1.5 times compared to room temperature.
“Lastly, we report that SARV increased at cryogenic temperature (by ~ 1.5 times) compared to room temperature (Fig. 6B).”
Quote in the paperNot a substantial claim - Findingown data
Porcine livers perfused with 40%EG + 0.6 M sucrose were vitrified, except for a small amount of ice around the portal vein and poorly vascularized perihilar/fatty tissue.
“Porcine livers (~0.6–1 L total volume; ~0.23–0.75 L organ volume) were also vitrified using EG+sucrose, though not rewarmed.”
- Also stated in: § Vitrification of a human-scale organ - porcine liver · hedged
“The liver appeared vitrified based on visual inspection, except for a small amount of ice formed around the portal vein and fatty tissue (poorly vascularized perihilar tissue), which presumably did not equilibrate fully with the CPA.”
Quote in the paperSubstantial claim - Also stated in: § Vitrification of a human-scale organ - porcine liver · hedged
- Findingown data
The calibration showed a linear relationship between applied power and field strength for the 120 kW coil.
“The calibration showed a linear relationship between applied power and field strength (Fig. 5C) for the 120 kW coil.”
Quote in the paperNot a substantial claim
- Findingown data
The magnetic field was spatially uniform within 5% for a 20 cm axial distance and 6 cm radial direction.
“The magnetic field was spatially uniform (within 5%) for a 20 cm axial distance and 6 cm radial direction (Fig. 5D).”
Quote in the paperSubstantial claim - Findingown data
Rewarming rates were identical when 0.5 L and 1 L volumes were rewarmed at the same IONP concentration.
“Rates were identical when 0.5 L and 1 L volumes were rewarming at the same IONP concentration (Fig. S22).”
Quote in the paperSubstantial claim - Findingown data
M22 vitrified successfully at 0.5, 1, and 3 L volumes.
“Successful vitrification in M22 was achieved for all volumes tested (Fig. 2).”
- Also stated in: § Introduction · plain
“We report the successful vitrification of volumes up to 3 L and uniform nanowarming from the vitrified cryogenic state of up to 2 L.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Findingown data
The minimum predicted and measured center cooling rate decreased with increased volume: ~1.4 °C/min for 0.5 L, ~1 °C/min for 1 L, and ~0.5 °C/min for 3 L.
“The minimum predicted and measured cooling rate (CR) (which is at the center) decreased with increased volumes from ~1.4 °C/min for 0.5 L (LC~1.2 cm) to ~1 °C/min for a 1 L (LC~1.4 cm) and finally ~0.5 °C/min for 3 L (LC~2.2 cm) cryobag.”
Quote in the paperSubstantial claim - Findingown data
40%EG + 0.6 M sucrose vitrified successfully with no visual ice formation up to 1 L.
“40%EG + 0.6Msucrose was also successfully vitrified with no visual ice formation up to 1 L (Fig. S10).”
Quote in the paperSubstantial claim - Findingown data
μCT images confirmed the absence of ice inside the liver tissue.
“µCT images further confirms the absence of ice inside the liver tissue (Fig. S15).”
Quote in the paperSubstantial claim - Findingown data
At full power, the 120 kW RF coil generated up to 35 kA/m magnetic field strength across the coil's volume at 360 kHz.
“At full power, the RF coil generated up to 35 kA/m magnetic field strength across the coil’s volume at a frequency of 360 kHz.”
Quote in the paperSubstantial claim - Findingown data
VS55 formed ice at all three volumes tested (0.5, 1, and 3 L).
“Ice formation was observed in VS55 for all three volumes (Fig. S8 and S10).”
Quote in the paperSubstantial claim - Findingown data
SARfe increased at higher frequencies (~2 times more at 360 kHz than 190 kHz for 35 kA/m).
“SARfe increased at higher frequencies (~2 times more at 360 kHz than 190 kHz for 35 kA/m), suggesting a proportional increase in heating with frequency, consistent with prior reports26,28,29.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [26] Etheridge, M. & Bischof, J. Optimizing magnetic nanoparticle based thermal therapies within the physical limits of heating. Ann. Biomed. Eng. 41, 78–88 (2013). source
- cites [28] Cao, M., Xu, Y. & Dong, Y. Improving Mechanical Properties of Vitrified Umbilical Arteries with Magnetic Warming. Fluid Dyn. Mater. Process. 17, 123–139 (2021). source
- cites [29] De la Presa, P. et al. Study of heating efficiency as a function of concentration, size, and applied field in γ-Fe2O3 nanoparticles. J. Phys. Chem. C. 116, 25602–25610 (2012). source
- Findingown data
Additional power in the larger RF coil was required to sustain the field uniformly across the higher coil volume (~80 mL versus 2.5 L).
“Additional power in the larger RF coil was required to sustain this field uniformly across the substantially higher coil volume (~80 mL versus 2.5 L).”
Quote in the paperNot a substantial claim - Findingown data
For the IONPs tested, SAR increased with magnetic field strength, saturating at higher field strengths.
“As seen in Fig. 6A, for the IONPs tested, SAR increased with magnetic field strength, though it saturated at higher field strengths, as observed elsewhere27.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Bordelon, D. E. et al. Magnetic nanoparticle heating efficiency reveals magneto-structural differences when characterized with wide ranging and high amplitude alternating magnetic fields. J. Appl. Phys., 109 (2011). source
- Findingreasoning
Higher heating and SARFe were found in the cryogenic regime.
“we find higher heating and SARFe in the cryogenic regime”
Quote in the paperNot a substantial claim - Findingnone given
The minimum CPA concentration needed for physical vitrification at 0.5 L (relevant for human kidneys and hearts) is at least ~8 M (40%EG + 0.6 M sucrose).
“The CPA concentration needed for physical vitrification at 0.5 L (relevant for human kidneys and hearts) is at least ~8 M (40%EG + 0.6Msucrose)”
Quote in the paperSubstantial claim - Findingreasoning
The amount of IONP required for nanowarming a human kidney can be estimated as ~0.4 gFe based on vascular fraction 0.2, organ volume 200 mL, and perfused IONP concentration 10 mgFe/mL.
“Using a human kidney as an example, the amount of IONP can be estimated as ~0.4 gFe = 0.2 (vascular fraction) * 200 mL (organ volume) * 10 mgFe/mL (perfused IONP concentration).”
Quote in the paperNot a substantial claim - Findingown data
The achieved cooling rates for 0.5, 1, and 3 L were lower than the CCR of VS55 (~2.5 °C/min).
“This was expected as the achieved cooling rate for these three volumes (0.5 L~1.4 °C/min, 1 L~1 °C/min, 3 L~0.5 °C/min) were lower than the CCR of VS55 (~2.5 °C/min).”
Quote in the paperSubstantial claim- Rests on an assumption: The critical cooling rate (CCR) of VS55 is ~2.5 °C/min.
- Findingown data
All predicted cooling rates are greater than those achieved experimentally in the successfully vitrified 3 L volume of M22 (~0.45 °C/min).
“Note that all predicted cooling rates are greater than those achieved experimentally in the successfully vitrified 3 L volume of M22 (cooling at ~0.45 °C/min).”
Quote in the paperNot a substantial claim - Findingcitation
The predicted nanowarming rate for adult human kidneys (40 °C/min) is lower than previously reported rates achieved in rat kidneys (>60 °C/min).
“the predicted nanowarming rate for adult human kidneys is lower than previously reported rates achieved in rat kidneys (40 °C/min versus >60 °C/min)15.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Han, Z. et al. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nat. Commun. 14, 3407 (2023). source
- Findingown data
Nanowarming provides uniform and scalable heating across various volumes.
“we have shown that nanowarming provides uniform and scalable heating across various volumes”
Quote in the paperSubstantial claim - Findingown data
M22 (~66% w/w including carrier solution) has successfully vitrified at 3 L.
“where we have shown successful vitrification at 3 L.”
Quote in the paperSubstantial claim - Findingown data
Heating 100 mg Fe/ml IONP in VMP reached rates up to ~1500 °C/min.
“We heated 100 mg Fe/ml IONP in VMP and reached rates up to ~1500 °C/min (Figs. S22 and 9C).”
Quote in the paperSubstantial claim - Findingown data
Average rewarming rates are greater than the CWR of M22 (~0.4 °C/min).
“Average rewarming rates are greater than the CWR of M22 (~0.4 °C/min).”
Quote in the paperSubstantial claim- Rests on an assumption: The critical warming rate (CWR) of M22 is ~0.4 °C/min.
- Findingreasoning
The minimum CPA concentration needed for physical vitrification at 3 L (relevant for human livers) is ~9.4 M (M22).
“and increases to ~9.4 M (M22) at 3 L scale (relevant for human livers) as the minimum expected cooling rates are below 1 °C/min (Table S6).”
Quote in the paperSubstantial claim - Findingown data
Nanowarming demonstrated uniform volumetric rewarming in volumes up to 2 L.
“We were able to demonstrate uniform volumetric rewarming using nanowarming in volumes up to 2 L.”
Quote in the paperSubstantial claim - Findingown data
Highly vascularized organs such as lungs (non-alveolar portions) and eyes will produce significantly higher nanowarming rates (~60 °C/min) than convection alone.
“Figure 9 also shows that highly vascularized organs such as lungs (non-alveolar portions) and eyes will produce significantly higher nanowarming rates (~60 °C/min) than convection alone”
Quote in the paperNot a substantial claim - Findingown data
Mean cooling rates are greater than the CCR of M22 (~0.1 °C/min).
“Mean cooling rates are greater than the CCR of M22 (~0.1 °C/min).”
Quote in the paperSubstantial claim- Rests on an assumption: The critical cooling rate (CCR) of M22 is ~0.1 °C/min.
- Interpretationown data
The difference in rewarming rates between 1 L and 2 L is due to ~50% lower IONP concentration in the larger 2 L bag.
“This difference is due to the use of ~50% lower IONP concentration in the larger 2 L bag.”
Quote in the paperSubstantial claim - Premisecitation
Rewarming rates scale linearly with IONP concentration.
“supporting prior observations that rewarming rates will scale linearly with IONP concentration29,31,32”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [29] De la Presa, P. et al. Study of heating efficiency as a function of concentration, size, and applied field in γ-Fe2O3 nanoparticles. J. Phys. Chem. C. 116, 25602–25610 (2012). source
- cites [31] Gao, Z. et al. Preparation of Scalable Silica-Coated Iron Oxide Nanoparticles for Nanowarming. Adv. Sci. 7, 1901624 (2020). source
- cites [32] Wakabayashi, T. et al. Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation. Bioeng. Transl. Med. 8, e10416 (2023). source
- Interpretationown data
This is the fastest nanowarming rate that has been measured that we are aware of.
“This is the fastest nanowarming rate that has been measured that we are aware of, supporting prior observations that rewarming rates will scale linearly with IONP concentration29,31,32, which is promising for future development.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [29] De la Presa, P. et al. Study of heating efficiency as a function of concentration, size, and applied field in γ-Fe2O3 nanoparticles. J. Phys. Chem. C. 116, 25602–25610 (2012). source
- cites [31] Gao, Z. et al. Preparation of Scalable Silica-Coated Iron Oxide Nanoparticles for Nanowarming. Adv. Sci. 7, 1901624 (2020). source
- cites [32] Wakabayashi, T. et al. Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation. Bioeng. Transl. Med. 8, e10416 (2023). source
- Interpretationown data
Human organ scale vitrification and rewarming is physically possible, as demonstrated by bulk systems equivalent in size to human organs being vitrified and nanowarmed.
“This work serves as a proof-of-concept that human organ scale vitrification and rewarming is physically possible, thereby enabling human organ banking in the future.”
- Also stated in: § Introduction · boosted
“This study demonstrates that bulk systems equivalent in size to human organs can be vitrified and nanowarmed, as verified by visual inspection, thermometry, and µCT.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · boosted
- Interpretationreasoning
The rates achieved in the small volume of rat kidneys likely included contributions from ambient warming and a higher IONP concentration in the surrounding CPA than was achieved solely due to the vascular fraction of the rat kidney.
“it is anticipated that the rates achieved in the small volume of rat kidneys included contributions from ambient warming and a higher IONP concentration in the surrounding CPA than was achieved solely due to the vascular fraction of the rat kidney.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Partial equilibration of perfused tissues to ~92-94% of full-strength CPA substantially increases the required cooling rates.
“which will substantially increase the required cooling rates.”
Quote in the paperSubstantial claim - Premisecitation
Convective cooling with liquid cryogens versus gaseous flow in CRF can enhance cooling rates due to larger heat transfer coefficients.
“due to larger heat transfer coefficients, convective cooling with liquid cryogens versus gaseous flow in CRF can enhance cooling rates24.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Incropera, F. P., et al., Fundamentals of heat and mass transfer. Vol. 6. Wiley New York. (1996)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation
The higher heating and SARFe in the cryogenic regime is likely due to higher susceptibility and magnetization at low temperatures and reduced specific heat of CPAs in the glassy region.
“likely due to the higher susceptibility and magnetization at such low temperatures and the reduced specific heat of CPAs in the glassy region13.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Etheridge, M. L. et al. RF heating of magnetic nanoparticles improves the thawing of cryopreserved biomaterials. Technology 2, 229–242 (2014). source
- Premisecitation
VS83 increases biological toxicity relative to the CPAs chosen here.
“but increase biological toxicity relative to the CPAs chosen here35.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] Han, Z. et al. Model-guided design and optimization of CPA perfusion protocols for whole organ cryopreservation. Ann. Biomed. Eng. 51, 2216–2228 (2023). source
- Premisecitation
Storing vitrified samples at a temperature far below Tg may induce more brittleness inside the samples.
“storing at a temperature far below Tg may also induce more brittleness inside the samples25.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Steif, P. S., Palastro, M. C. & Rabin, Y. The effect of temperature gradients on stress development during cryopreservation via vitrification. Cell Preserv. Technol. 5, 104–115 (2007). source
- Premisecitation
Experimental work on dilutions of VMP and VS55 in tissue shows similar vitrifiability to 100% CPA.
“experimental work on such dilutions of VMP and VS55 in tissue show similar vitrifiability to 100% CPA48.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] Han, Z. et al. Kidney tissue loading reduces the critical cooling and warming rates of VS55 and VMP cryoprotective solutions. Cryobiology 117, 104977 (2024). source
- Premisecitation
Vitrification has been attempted up to 1.5 L but failed due to ice formation and fracture.
“Since then, vitrification has been attempted up to 1.5 L but failed due to underlying ice formation and fracture5, inherent to heat transfer at these scales.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Fahy, G. M., Saur, J. & Williams, R. J. Physical problems with the vitrification of large biological systems. Cryobiology 27, 492–510 (1990). source
- Interpretationown data
Nanowarming offers substantial increases in rates and uniformity of heating for large organs.
“While nanowarming offers substantial increases in rates and uniformity of heating for large organs”
Quote in the paperSubstantial claim - Premisecitation
The thermal expansion coefficient of M22 (~2.52 × 10−4) is greater than that of VS55 (~1.84 × 10−4).
“the thermal expansion coefficient of M22 (~2.52 × 10−4) is greater than VS55 (~1.84 × 10−4)43”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] Solanki, P. K. & Rabin, Y. Perspective: temperature-dependent density and thermal expansion of cryoprotective agents. CryoLetters 43, 1–9 (2022). source
- Study design and conductown data
Physical vitrification was verified by transparency observed by visual inspection and photography.
“Physical vitrification was verified by transparency observed by visual inspection and photography.”
Quote in the paperSubstantial claim - Interpretationown data
Larger organ systems will likely achieve the greatest benefits from nanowarming.
“larger organ systems will likely achieve the greatest benefits.”
Quote in the paperSubstantial claim - Study design and conductown data
Due to the limitations of the 120 kW RF coil diameter, none of the vitrified livers in this study were nanowarmed.
“due to the limitations of the 120 kW RF coil diameter (Fig. S24), none of the vitrified livers in this study were nanowarmed.”
Quote in the paperSubstantial claim - Study design and conductreasoning
No biological assessment of the organ was performed in this study.
“No biological assessment of the organ was performed”
Quote in the paperSubstantial claim - Interpretationreasoning
Heating is practically uniform if the magnetic field is uniform, because heat rapidly diffuses across intercapillary distances given the timescales of rewarming.
“Given the timescales of rewarming, heating is practically uniform if the magnetic field is uniform, as the heat rapidly diffuses across intercapillary distances.”
Quote in the paperSubstantial claim- Rests on an assumption: Heat rapidly diffuses across intercapillary distances given the timescales of rewarming.
- Interpretationown data
The minimum cooling rates to avoid ice formation during vitrification of different human organs can be predicted based on their characteristic length (LC).
“As a useful first-order approximation, the minimum cooling rates to avoid ice formation during the vitrification of different human organs can be predicted based on their characteristic length (LC) (Fig. 8A, Table S6, supplementary section on cooling rate calculation).”
Quote in the paperSubstantial claim - Interpretationreasoning
The 120 kW RF coil substantially extends capabilities beyond previous nanowarming studies.
“This substantially extends our capabilities beyond previous nanowarming studies (Fig. 5).”
Quote in the paperSubstantial claim - Interpretationreasoning
Since nanowarming rates are independent of sample volume, cooling conditions will become the rate-limiting step in vitrifying and rewarming human organ-scale volumes.
“It is also important to note that since nanowarming rates are independent of sample volume, cooling conditions will become the rate-limiting step in vitrifying and rewarming human organ-scale volumes.”
Quote in the paperSubstantial claim - Interpretationreasoning
Nanowarming is fully scalable to human organs in theory because RF waves penetrate without significant attenuation.
“Since the chosen radiofrequency waves penetrate the system without significant attenuation, this approach is, in theory, fully scalable to human organs.”
Quote in the paperSubstantial claim - Premisecitation
During CPA perfusion loading of organs, successfully perfused tissues may only equilibrate to ~92-94% concentration of full-strength CPA.
“during CPA perfusion loading of organs, successfully perfused tissues may only equilibrate to ~92-94% concentration of full-strength CPA15,34”
- Also stated in: § Discussion · hedged
“tissue equilibration is often only in the range of ~92–94% after organ perfusion15,34”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] Han, Z. et al. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nat. Commun. 14, 3407 (2023). source
- cites [34] Fahy, G. M. et al. Physical and biological aspects of renal vitrification. Organogenesis 5, 167–175 (2009). source
- Also stated in: § Discussion · hedged
- Premisecitation
HIFU is currently limited to volumes ≤2 mL.
“HIFU heats by focusing sound/pressure waves on the vitrified material but is currently limited to volumes ≤2 mL7.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] Olmo, A. et al. The use of high-intensity focused ultrasound for the rewarming of cryopreserved biological material. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 68, 599–607 (2020). source
- Interpretationreasoning
Without proper annealing, vitrified samples are more susceptible to fracture during cryogenic storage and rewarming.
“Without proper annealing, these samples will be more susceptible to fracture during cryogenic storage and rewarming.”
Quote in the paperSubstantial claim- Rests on an assumption: Cracking is a major mode of physical injury during organ vitrification.
- Premisecitation
Dielectric/microwave rewarming potential volumes can approach ~100 mL in CPA systems, including rabbit kidneys (~50 mL).
“Dielectric/microwave rewarming (heating of dipolar molecules by electromagnetic (EM) waves) potential rewarming volumes can approach ~100 mL in CPA systems10, including rabbit kidneys (~50 mL)11.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [10] Ruggera, P. S. & Fahy, G. M. Rapid and uniform electromagnetic heating of aqueous cryoprotectant solutions from cryogenic temperatures. Cryobiology 27, 465–478 (1990). source
- cites [11] Wowk, B. et al. 27 MHz constant field dielectric warming of kidneys cryopreserved by vitrification. Cryobiology 115, 104893 (2024). source
- Interpretationown data
Eddy current heating is expected to be insignificant at cryogenic temperatures, especially in the vitrified glassy state.
“eddy current heating is expected to be insignificant at cryogenic temperatures, especially in the vitrified glassy state”
Quote in the paperSubstantial claim
- It may state two separate claims as one. 21
- The quote only partly states this claim. 1
- Probably not a substantial claim. 20
It may state two separate claims as one.
Findingown dataModeling predicted the center cooling rate of the porcine liver as ~4 °C/min, exceeding the CCR (~1 °C/min) of 40%EG + 0.6 M sucrose.
“Modeling predicted the center cooling rate of the liver as ~4 °C/min, which exceeds the CCR (~1 °C/min) of 40%EG + 0.6Msucrose, which further supports vitrification (see Fig. S6).”
Quote in the paperSubstantial claim- Rests on an assumption: The critical cooling rate (CCR) of 40%EG + 0.6 M sucrose is ~1 °C/min.
It may state two separate claims as one.
Findingown dataUniform nanowarming was achieved in 1 L and 2 L volumes of M22, with rewarming rates of ~172 °C/min for 1 L and ~88 °C/min for 2 L, and temperature differences <5 °C.
“Using nanowarming with iron-oxide nanoparticles and a newly developed 120 kW RF coil, uniform rewarming was achieved in up to 2 L volumes of M22 at ~88 °C/min.”
- Also stated in: § Liter scale nanowarming · plain
“Samples were rewarmed to 0°C within ~1 min for 1 L and ~2 min for 2 L at rates of ~172 °C/min and ~88 °C/min, respectively (Fig. 7C).”
- Also stated in: § Liter scale nanowarming · plain
“In all cases, the measured temperature differences across the cryobag volume were negligible (~<5°C) (Fig. 7D).”
Quote in the paperSubstantial claim- Also stated in: § Liter scale nanowarming · plain
It may state two separate claims as one.
Findingown dataEffective cryobag sealing was beneficial in preventing open-surface ice formation and reducing the size of the system (LC).
“Effective cryobag sealing was beneficial in preventing open-surface ice formation and reducing the size of the system (LC).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataCooling rates decreased and temperature differences increased with increasing sample volume.
“As before, the cooling rates decreased, and the temperature differences increased with increasing sample volume.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataμCT confirmed successful vitrification in M22 and 40%EG + 0.6 M sucrose but ice formation in VS55 at 0.5 L.
“We further confirmed our visual findings using µCT, which showed successful vitrification in M22 and 40%EG + 0.6Msucrose but ice formation in VS55 at 0.5 L volumes (Fig. S13).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataNanowarming of 100 mgFe/mL EMG308 IONPs in VMP CPA in a 1 mL cryovial achieved warming rates of ~1500 °C/min.
“We achieved warming rates at ~1500 °C/min (Fig. S22).”
- Also stated in: § Liter scale nanowarming · plain
“As a final proof of principle, we nanowarmed a higher concentration of IONP (100 mgFe/mL EMG308) using VMP as the CPA (closely related to M22) in a 1 mL cryovial30.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] Fahy, G. M. et al. Improved vitrification solutions based on the predictability of vitrification solution toxicity. Cryobiology 48, 22–35 (2004). source
- Also stated in: § Liter scale nanowarming · plain
It may state two separate claims as one.
Findingown dataThe maximum field strength and frequency output were comparable between the 15 kW and 120 kW systems.
“Importantly, the maximum field strength and frequency output were comparable between the 15 kW and 120 kW systems.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
FindingreasoningA small organ such as an ovary can convectively cool at ~15 °C/min, whereas the center of a liver is only expected to cool at ~0.6 °C/min.
“For instance, a small organ such as an ovary can convectively cool at ~15 °C/min, whereas the center of a liver is only expected to cool at ~0.6 °C/min (these calculations assume the organ is vitrified alone without any surrounding CPA, but LC could be adjusted for individual container geometries).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataVacuum sealing with removal of surrounding CPA solution led to ice on superficial surfaces of the liver, potentially due to cryobag surface nucleation, so having a layer of CPA around the liver in the bag proved beneficial for successful vitrification.
“Vacuum sealing with the removal of surrounding CPA solution led to ice on superficial surfaces of the liver, potentially due to cryobag surface nucleation, so having a layer of CPA around the liver in the bag proved beneficial for successful vitrification.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataFor a human kidney, perfused IONP concentration of ~10 mgFe/mL will provide a rewarming rate of ~40 °C/min, which is safely above the CWR of M22.
“Fig. 9 shows that for a human kidney, perfused IONP concentration of ~10 mgFe/mL will provide a rewarming rate of ~40 °C/min, which is safely above the CWR of M22.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingnone givenAchievable convective rewarming rates may be higher (~2 times) for small, less vascularized organs (e.g., ovaries and testes).
“achievable convective rates may be higher (~2 times) for small, less vascularized organs (e.g., ovaries and testes).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
FindingreasoningFor 3 L, the calculated characteristic length LC is ~2.2 cm and the expected cooling rate in the CRF is <0.8 °C/min.
“for 3 L we can calculate LC ~ 2.2 cm and the expected CR in the CRF to be <0.8 °C/min.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Study design and conductown dataA 120 kW RF coil with a 2.5 L uniform field region was designed, built, and characterized.
“we worked with AMF LifeSystems, LLC. to design, build, and characterize a 120 kW RF coil with a 2.5 L uniform field region.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductcitationSAR was calculated using the time rise method described elsewhere.
“SAR was then calculated using the time rise method described elsewhere26,52 (see supplementary SAR section, Fig. S19).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [26] Etheridge, M. & Bischof, J. Optimizing magnetic nanoparticle based thermal therapies within the physical limits of heating. Ann. Biomed. Eng. 41, 78–88 (2013). source
- cites [52] Ring, H. L. et al. The impact of data selection and fitting on SAR estimation for magnetic nanoparticle heating. Int. J. Hyperth. 37, 100–107 (2020). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown dataRF coil performance was characterized by measuring the spatial distribution across the full range of magnetic field values.
“Performance was characterized by measuring the spatial distribution across the full range of magnetic field values.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
InterpretationcitationAdditional ice nucleation may have occurred during storage of VS55 just below Tg.
“suggesting additional ice nucleation may have occurred during storage.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenTemperature probes were pre-calibrated for any offset in the cryogenic temperature range.
“The probes were pre-calibrated for any offset in the cryogenic temperature range.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown dataHigher rewarming rates will be possible at higher IONP concentrations or with higher heating nanoparticles.
“Higher rewarming rates will also be possible at higher IONP concentrations or with higher heating nanoparticles.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
Study design and conductnone givenThe custom-made cooler can hold samples at cryogenic temperatures in a vitrified state (<Tg).
“The custom-made cooler can hold samples at cryogenic temperatures in a vitrified state (<Tg).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown dataExperimental test points showing success of M22, EG+Sucrose, and failure of VS55 at various LC validate the first-order approximation.
“The experimental test points (x) showing success of M22, EG+Sucrose, and failure of VS55 at various LC (0.5, 1, 3 L volumes) are also plotted in B, validating the first-order approximation.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationOther nanomaterials, such as nanowires/nanobars, have shown ultra-rapid nanowarming heating rates up to ~1000 °C/min at much lower nanoparticle concentrations in proof-of-principle cryovial (<1 mL) samples.
“other nanomaterials, such as nanowires/nanobars, have also shown ultra-rapid nanowarming heating rates up to ~1000 °C/min at much lower nanoparticle concentrations in proof of principle cryovial (<1 mL) samples (e.g., Cobalt Nickel nanowires in VS55)45.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] Shore, D. et al. Nanowarming using Au-tipped Co35Fe65 ferromagnetic nanowires. Nanoscale 11, 14607–14615 (2019). source
It may state two separate claims as one.
PremisecitationTo achieve cryopreservation of human organs through vitrification, 0.5−1 L volumes are anticipated for hearts and kidneys, while human livers may require ≥3 L.
“To achieve cryopreservation of human organs through vitrification, we anticipate needing 0.5−1 Liter volumes for hearts and kidneys, while human livers may require ≥3 L20.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Hall, C., Lueshen, E. & Linninger, A. A. Interspecies scaling in pharmacokinetics: a novel whole-body physiologically based modeling framework to discover drug biodistribution mechanisms in vivo. J. Pharm. Sci. 101, 1221–1241 (2012). source
It may state two separate claims as one.
PremisecitationEven under conditions where vitrification upon cooling was successful, even faster rates are required upon rewarming, leading to failures at the rabbit kidney scale.
“Even under conditions where vitrification upon cooling was successful, even faster rates are required upon rewarming, leading to failures (ice formation and/or cracking) at the rabbit kidney scale6.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Manuchehrabadi, N. et al. Improved tissue cryopreservation using inductive heating of magnetic nanoparticles. Sci. Transl. Med. 9, eaah4586 (2017). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown dataModeled and experimentally measured magnetic field distributions were used to compare spatial uniformity between the 15 kW and 120 kW RF coils.
“We used modeled as well as experimentally measured magnetic field distribution to compare spatial uniformity between the previously characterized 15 kW6 and the new 120 kW RF coils (Fig. S16).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] Manuchehrabadi, N. et al. Improved tissue cryopreservation using inductive heating of magnetic nanoparticles. Sci. Transl. Med. 9, eaah4586 (2017). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown dataThe colloidal stability of sIONPs and EMG308 in M22 was monitored by dynamic light scattering.
“The colloidal stability of sIONPs and EMG308 in M22 was monitored by dynamic light scattering (DLS, see Fig. S1).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
InterpretationreasoningThe minimum CPA concentration for vitrification at 3 L is ~62% w/w, slightly lower than M22 (~66% w/w including carrier solution).
“Hence, the minimum CPA concentration for vitrification would be ~62% w/w, which is slightly lower than M22 (~66%w/w which includes carrier solution)”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationStorage of VS55 for 6 months just below Tg increased CWR from 50 to ~100 °C/min.
“storage of VS55 for 6 months just below Tg increased CWR from 50 to ~100 °C/min40”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] Mehl, P. M. Nucleation and crystal growth in a vitrification solution tested for organ cryopreservation by vitrification. Cryobiology, 30. (1993) source
It may state two separate claims as one.
PremisecitationVS83 (83% w/w CPA) has lower CCR and can be more easily vitrified than the CPAs chosen here.
“Higher concentrations of CPAs such as VS83 (83% w/w CPA) have even lower CCR and can be more easily vitrified”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Han, Z. et al. Model-guided design and optimization of CPA perfusion protocols for whole organ cryopreservation. Ann. Biomed. Eng. 51, 2216–2228 (2023). source
Probably not a substantial claim.
Study design and conductreasoningThe recommended protocols were designed so that the temperature difference within the glassy state is less than 20 °C to avoid fracture.
“Further, the ∆T within the glassy state was designed to be less than 20 °C, to avoid fracture.”
Quote in the paperSubstantial claimProbably not a substantial claim.
PremisecitationA temperature difference <20 °C in the brittle glassy phase is an allowable limit.
“After annealing, the system was cooled slowly (<1 °C/min) to −150 °C for storage to minimize thermal stress, keeping the temperature difference (<20 °C) in the brittle glassy phase21,25.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [21] Gangwar, L. et al. Perspective: A Guide to Successful ml to L Scale Vitrification and Rewarming. CryoLetters 43, 303–315 (2022). source
- cites [25] Steif, P. S., Palastro, M. C. & Rabin, Y. The effect of temperature gradients on stress development during cryopreservation via vitrification. Cell Preserv. Technol. 5, 104–115 (2007). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenThe University of Minnesota's IACUC approved this study.
“The University of Minnesota’s Institutional Animal Care and Use Committee (IACUC) approved this study.”
- Also stated in: § Ethical declaration · plain
“The Institutional IACUC committee from the University of Minnesota (protocol #2111A39564) approved all animal studies.”
Quote in the paperNot a substantial claim- Also stated in: § Ethical declaration · plain
It may state two separate claims as one.
PremisecitationFor long-term storage of human organ-scale vitrified samples, physical aging of the glass can elevate Tg, decrease Td, and increase heat release at the glass transition during rewarming.
“For long-term storage (days to months to years) of human organ-scale vitrified samples, physical aging of the glass can also elevate Tg, decrease Td (devitrification temperature), and increase heat release at the glass transition during rewarming from the vitrified state41,42.”
Quote in the paperNot a substantial claim0 of 2 sources checkedIt may state two separate claims as one.
PremisecitationThere are currently no volumetric means of cooling human organs, so convective cooling will be directly impacted by the size of the system, with the cooling rate at the center decreasing as size increases.
“There are currently no volumetric means of cooling human organs, so convective cooling will be directly impacted by the size of the system, with the cooling rate at the center of the sample decreasing as the size of the system increases21.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Gangwar, L. et al. Perspective: A Guide to Successful ml to L Scale Vitrification and Rewarming. CryoLetters 43, 303–315 (2022). source
Probably not a substantial claim.
Study design and conductnone givenThe recommended annealing and glassy region cooling rate protocols were designed to be faster than the CCR of the noted CPAs between the melt and glass transitions.
“These protocols were designed to be faster than the CCR of the noted CPAs between the melt and glass transitions.”
Quote in the paperSubstantial claimProbably not a substantial claim.
Study design and conductnone givenA total of ≥3 replicates were conducted for all cooling, nanowarming, and SAR experiments.
“A total of ≥3 replicates are conducted for all the cooling, nanowarming, and SAR experiments.”
Quote in the paperSubstantial claimProbably not a substantial claim.
Study design and conductown dataMicrocomputed tomography (μCT) was used to verify physical vitrification.
“Microcomputed tomography (µCT) was used to verify physical vitrification (Fig. S13, S15).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
InterpretationcitationThis may lead to insufficient cooling rates and/or physical fractures/cracking due to thermal gradients in the vitrified state if a proper cooling protocol is not employed.
“This may lead to insufficient cooling rates and/or physical fractures/cracking due to thermal gradients in the vitrified state22 if a proper cooling protocol is not employed.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Rabin, Y. et al. Fracture formation in vitrified thin films of cryoprotectants. Cryobiology 53, 75–95 (2006). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
InterpretationreasoningM22 might be more prone to fractures from thermal stress because it has a greater thermal expansion coefficient and polymers that may be more thermally expansive.
“which could mean that M22 (which has polymers that may be more thermally expansive44) might be more prone to fractures from thermal stress.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Holliday, L. & Robinson, J. The thermal expansion of composites based on polymers. J. Mater. Sci. 8, 301–311 (1973). source
- Rests on an assumption: CPA constituents (polymers, sugars, salts, etc.) can impact stability in the brittle (glassy) state.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
InterpretationreasoningA lack of uniformity during convective rewarming may still lead to cracking in small, less vascularized organs.
“However, a lack of uniformity during convective rewarming may still lead to cracking in these cases.”
Quote in the paperNot a substantial claim- Rests on an assumption: Cracking is a major mode of physical injury during organ vitrification.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
InterpretationreasoningNanowires/nanobars may be limited to external heating due to their aspect ratio, size, and biocompatibility concerns.
“Still, these may be limited to external heating due to their aspect ratio, size, and concerns regarding biocompatibility.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductnone givenReplicates were performed on different days with distinct samples for livers and the same samples on different days for CPA experiments.
“Replicates were performed on different days with distinct samples for livers and the same samples on different days for CPA experiments.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Neither successful vitrification nor rewarming has been demonstrated in the literature at human organ scales (0.5–3 L).
“However, neither successful vitrification nor rewarming has been demonstrated in the literature at these scales.”
The paper relies on this without support.
Capillary spacing is relatively conserved across organs and tissues, and uniformity and heating rate depend primarily on IONP concentration, magnetic field strength distribution, and frequency.
“Since capillary spacing is relatively conserved across organs and tissues, uniformity and heating rate depend primarily on the concentration of IONPs, distribution of the magnetic field strength, and frequency.”
The authors state this as an assumption.
The thermal properties of M22 are a reasonable approximation for the other CPAs (VS55 and 40%EG + 0.6 M sucrose).
“Limited data on CPA thermal properties are available, hence we assume them to be that of M22 (listed in Table S2)23, which should be a reasonable approximation for each of the other CPAs.”
The paper relies on this without support.
Convection within the CPA itself is neglected due to the high viscosity of CPAs at subzero temperatures.
“Convection within the CPA itself is neglected due to the high viscosity of CPAs at subzero temperatures.”
The paper relies on this without support.
The critical cooling rate (CCR) of M22 is ~0.1 °C/min.
“Mean cooling rates are greater than the CCR of M22 (~0.1 °C/min).”
The paper relies on this without support.
The critical cooling rate (CCR) of VS55 is ~2.5 °C/min.
“This was expected as the achieved cooling rate for these three volumes (0.5 L~1.4 °C/min, 1 L~1 °C/min, 3 L~0.5 °C/min) were lower than the CCR of VS55 (~2.5 °C/min).”
The paper relies on this without support.
The critical cooling rate (CCR) of 40%EG + 0.6 M sucrose is ~1 °C/min.
“Modeling predicted the center cooling rate of the liver as ~4 °C/min, which exceeds the CCR (~1 °C/min) of 40%EG + 0.6Msucrose, which further supports vitrification (see Fig. S6).”
The paper relies on this without support.
The critical warming rate (CWR) of M22 is ~0.4 °C/min.
“Average rewarming rates are greater than the CWR of M22 (~0.4 °C/min).”
The authors state this as an assumption.
IONP distributions are practically uniform through vascular perfusion to the capillary beds.
“As noted earlier, uniformity in rewarming will depend on the uniformity of the applied field, assuming practically uniform IONP distributions (i.e., through vascular perfusion to the capillary beds).”
The paper relies on this without support.
Heat rapidly diffuses across intercapillary distances given the timescales of rewarming.
“as the heat rapidly diffuses across intercapillary distances.”
The authors state this as an assumption.
Organs can be approximated as ellipsoidal shapes for LC calculation.
“LC is calculated for various organs assuming ellipsoidal shape, and minimum cooing rate occurs at the center of geometry.”
The authors state this as an assumption.
The minimum cooling rate occurs at the center of the geometry.
“LC is calculated for various organs assuming ellipsoidal shape, and minimum cooing rate occurs at the center of geometry.”
The paper relies on this without support.
Cracking is a major mode of physical injury during organ vitrification.
“The other major mode of physical injury during organ vitrification is cracking.”
The paper relies on this without support.
CPA constituents (polymers, sugars, salts, etc.) can impact stability in the brittle (glassy) state.
“Further, CPA constituents (polymers, sugars, salts, etc.) can also impact stability in the brittle (i.e., glassy) state.”
The authors state this as an assumption.
CPA would fully equilibrate in tissue.
“we assumed that CPA would fully equilibrate in tissue”
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.
CPA replicates described as both distinct and reused samples
MinorThe Fig. 7 legend describes the M22 nanowarming experiments as using distinct samples, whereas the data-analysis section says CPA experiments reused the same samples on different days.
“Scatter plots of c average rewarming rate and d temperature difference (∆T) for 1 L and 2 L M22 (mean ± SD; n = 3 independent experiments from distinct samples).”
“Replicates were performed on different days with distinct samples for livers and the same samples on different days for CPA experiments.”
Citations
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Nanowarming using Au-tipped Co 35 Fe 65 ferromagnetic nanowires
Shore, D., Ghemes, A., Dragos-Pinzaru, O., Gao, Z., Shao, Q., Sharma, A., Um, J., Tabakovic, I., Bischof, J. C., & Stadler, B. J. H. (2019) · Nanoscale · doi:10.1039/c9nr01182j · Cited by 42
Self-citationThe impact of data selection and fitting on SAR estimation for magnetic nanoparticle heating
Ring, H. L., Sharma, A., Ivkov, R., & Bischof, J. C. (2020) · International Journal of Hyperthermia · doi:10.1080/02656736.2020.1810332 · Cited by 40
Self-citationPhysical aging of glassy state: DSC study of vitrified glycerol systems
Chang, Z. H., & Baust, J. G. (1991) · Cryobiology · doi:10.1016/0011-2240(91)90010-l · Cited by 37
Diffusion Limited Cryopreservation of Tissue with Radiofrequency Heated Metal Forms
Han, Z., Sharma, A., Gao, Z., Carlson, T. W., O’Sullivan, M. G., Finger, E. B., & Bischof, J. C. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000796 · Cited by 37
Self-citationThermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification
Ehrlich, L. E., Fahy, G. M., Wowk, B. G., Malen, J. A., & Rabin, Y. (2017) · Journal of Biomechanical Engineering · doi:10.1115/1.4037406 · Cited by 36
Wowk, B. G., Fahy, G. M., Ahmedyar, S., Taylor, M. J., & Rabin, Y. (2018) · Cryobiology · doi:10.1016/j.cryobiol.2018.04.006 · Cited by 35
27 MHz constant field dielectric warming of kidneys cryopreserved by vitrification
Wowk, B., Phan, J., Pagotan, R., Galvez, E., & Fahy, G. M. (2024) · Cryobiology · doi:10.1016/j.cryobiol.2024.104893 · Cited by 32
Zhan, T., Liu, K., Yang, J., Dang, H., Chen, L., & Xu, Y. (2021) · ACS Applied Nano Materials · doi:10.1021/acsanm.1c03014 · Cited by 26
GUTTMAN, F. M., Khalessi, A. A., Huxley, B. W., Lee, R., & Savard, G. (1969) · Cryobiology · doi:10.1016/s0011-2240(69)80005-2 · Cited by 24
Experiments and simulations demonstrating the rapid ultrasonic rewarming of frozen tissue cryovials
Xu, R., Treeby, B. E., & Martin, E. M. (2023) · The Journal of the Acoustical Society of America · doi:10.1121/10.0016886 · Cited by 22
Model-Guided Design and Optimization of CPA Perfusion Protocols for Whole Organ Cryopreservation
Han, Z., Rao, J. S., Ramesh, S., Hergesell, J., Namsrai, B.-E., Etheridge, M. L., Finger, E. B., & Bischof, J. C. (2023) · Annals of Biomedical Engineering · doi:10.1007/s10439-023-03255-5 · Cited by 21
Self-citationThe Use of High-Intensity Focused Ultrasound for the Rewarming of Cryopreserved Biological Material
Olmo, A., Barroso, P., Barroso, F., & Risco, R. (2021) · IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control · doi:10.1109/tuffc.2020.3016950 · Cited by 20
Perspective: Temperature-Dependent Density And Thermal Expansion Of Cryoprotective Agents
Solanki, P. K., & Rabin, Y. (2022) · Cryoletters · doi:10.54680/fr22110110112 · Cited by 20
Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation
Wakabayashi, T., Kaneko, M., Nakai, T., Horie, M., Fujimoto, H., Takahashi, M., Tanoue, S., & Ito, A. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10416 · Cited by 18
Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples
Pasek-Allen, J. L., Wilharm, R. K., Gao, Z., Pierre, V. C., & Bischof, J. C. (2022) · Journal of Materials Chemistry B · doi:10.1039/d1tb02483c · Cited by 17
Self-citationPerspective: A Guide to Successful ml to L Scale Vitrification and Rewarming
Gangwar, L., Phatak, S. S., Etheridge, M., & Bischof, J. C. (2022) · Cryoletters · doi:10.54680/fr22610110112 · Cited by 17
Self-citationImproving Mechanical Properties of Vitrified Umbilical Arteries with Magnetic Warming
Cao, M., Xu, Y., & Dong, Y. (2021) · Fluid Dynamics & Materials Processing · doi:10.32604/fdmp.2021.011443 · Cited by 12
CPA toxicity screening of cryoprotective solutions in rat hearts
Kraft, C., Namsrai, B., Tobolt, D. K., Etheridge, M. L., Finger, E. B., & Bischof, J. C. (2023) · Cryobiology · doi:10.1016/j.cryobiol.2023.104842 · Cited by 6
Self-citationHan, Z., Gangwar, L., Namsrai, B.-E., Rao, J. S., Scheithauer, C., Etheridge, M. L., Finger, E. B., Bischof, J. C., & Choi, J. (2024) · Cryobiology · doi:10.1016/j.cryobiol.2024.104977 · Cited by 6
Self-citationA guide to successful mL to L scale vitrification and rewarming.
Gangwar, L., Phatak, S., Etheridge, M. L., & Bischof, J. C. (2022) · PubMed · Cited by 3
Self-citation
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
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Cited by
Sorted by citations
55 MHz constant field dielectric warming of kidneys and ovaries cryopreserved by vitrification
Wowk, B. G., Ting, A. Y., Phan, J., Pagotan, R., Sharif, A., Chow, L., & Fahy, G. M. (2025) · Cryobiology · doi:10.1016/j.cryobiol.2025.105257 · Cited by 13
Ma, R., Wang, Z., Shen, R., Shu, Z., Chen, M., & Gao, D. Y. (2025) · Frigid Zone Medicine · doi:10.1515/fzm-2025-0010 · Cited by 4
Oziri, O. J., Scheithauer, C., Wong, H. L., Etheridge, M. L., Finger, E. B., & Bischof, J. C. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04471-6 · Cited by 4
Self-citationGangwar, L., Jiang, Y., Thunberg, D., Scheithauer, C., Etheridge, M. L., Bischof, J. C., & Franklin, R. (2025) · Scientific Reports · doi:10.1038/s41598-025-07207-y · Cited by 4
Self-citationKe, T., Fan, X., Zheng, S., Liu, X., Sun, H., Fan, H., Yang, M., Lu, Q., Xie, H., Zhou, H., et al. (2025) · Advanced Materials · doi:10.1002/adma.202515996 · Cited by 3
Electric fields for warming cryopreserved tissue
Wowk, B. G. (2026) · Cryobiology · doi:10.1016/j.cryobiol.2026.105627 · Cited by 2
REVIEW OF BULK CRYOPRESERVATION ENABLED BY NANOWARMING
Gangwar, L., Han, Z., Oziri, O. J., Ramesh, S., Etheridge, M. L., Finger, E. B., & Bischof, J. C. (2024) · Annual Reviews of Heat Transfer · doi:10.1615/annualrevheattransfer.2024055273 · Cited by 1
Self-citationUltrasonic rewarming of cryopreserved alginate encapsulated liver spheroids
Xu, R., Brookshaw, T., Erro, E., Selden, C., & Martin, E. M. (2025) · Scientific Reports · doi:10.1038/s41598-025-21464-x · Cited by 1
Repurposing ferumoxytol as a nanowarming agent for vitrification-based organ preservation
Feng, H., Mao, Y., Zhang, Y., Si, G., Lu, K., Zheng, M., Ni, W., Li, Y., Huang, Y., Zhang, M., et al. (2026) · Nano Today · doi:10.1016/j.nantod.2026.102981 · Cited by 1
Barsukova, A. D., Weng, L., Szymanska-Vandendriessche, K. J., Scott, M., Langer, R., & Traverso, G. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114914 · Cited by 1
Hou, Y. K., Yang, F., Li, Z., & Rao, W. (2026) · Journal of Medical Devices · doi:10.1115/1.4070896
Thermodynamic Principles of Emerging Cryopreservation Technologies
Powell‐Palm, M. J., & Consiglio, A. N. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5416-3_4
Hydrogen-Bond Exchange Governs Opposite Vitrification Behaviors in Cryoprotectant Solutions
Lin, M., & Cao, H. (2026) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.6c00913
A guide to cryogenic refrigerant properties and selection for tissue & organ cryopreservation
Gangwar, L., Haggard, D. M., Etheridge, M. L., Shiflett, M. B., & Bischof, J. C. (2026) · Cryobiology · doi:10.1016/j.cryobiol.2026.105643
Self-citationAhmadkhani, N., Sugden, C., Lee, E., Baiz, C. R., Brown, D., Drummond, N., Snyder, A., Uden, M., & Higgins, A. Z. (2026) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6c06194
Low-toxicity vitrification of small-diameter arterial grafts by achieving a Cryo-Stasis state
Zhao, Z., Zhang, B., & Zhao, G. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103439
Salve, C., Bohra, S., More, A., & Singh, B. (2026) · International Journal of Health & Allied Sciences · doi:10.4103/ijhas.ijhas_97_26
Thermomechanics analysis of cryopreservation by vitrification of the popliteal artery
Vispute, D. M., & Rabin, Y. (2026) · PLoS ONE · doi:10.1371/journal.pone.0350078
Hu, Y., Liu, Y., Wu, X., Wang, Z., & Zhao, G. (2026) · International Journal of Heat and Mass Transfer · doi:10.1016/j.ijheatmasstransfer.2026.129498
Nanowarming: Using Molecular Nanotechnology to Make Organ Banking Possible
Skow, A. (2026) · Truth in Research · doi:10.67690/tbfhva49
Wilczok, D., Long, Q., Huang, Z., Kangas, J. R., Liu, Y., Wang, M., & Kappes, F. (2026) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2026.102782
Advanced Rewarming Technologies for Cryopreservation
Wang, Z., Hao, S., Jin, Y., Ma, X., Ma, R., Ren, S., Gao, D. Y., & Shu, Z. (2026) · Methods in molecular biology · doi:10.1007/978-1-0716-5416-3_6
Kassier, A. B., Javed, H., Zaghw, A., Rogers, M. O., Coffield, S., Have, G. A. M. T., & Rajab, T. K. (2026) · Cryobiology · doi:10.1016/j.cryobiol.2026.105716
Functional recovery of vitrified and nanowarmed human-scale pig kidneysPreprint
Zonghu, 韩. H., Namsrai, B., Chimedtseren, A., Chen, A. A. D., Fisher, B. J., Tobolt, D. K., Megaly, M. G., Oziri, O. J., Jiang, M., Rao, J. S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.07.756990
Self-citationNanotechnology-driven cryopreservation across cells and 3D constructs
Kim, J., Jang, Y., & Park, H. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.104059
Logistics of clinical xenotransplantation: from donor pig production to global organ distribution
Fischer, K., Denner, J., Tönjes, R. R., Felgendreff, P., & Rahmel, A. O. (2026) · Transplant International · doi:10.3389/ti.2026.17326
Metadata
- Authors
- Gangwar, L., Han, Z., Scheithauer, C., Namsrai, B.-E., Kantesaria, S., Goldstein, R., Etheridge, M. L., Finger, E. B., & Bischof, J. C.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Finger, Erik B.
- Bischof, John C.
- ORCID
- Venue
- Nature Communications
- Published
- 2025-09-26
- Volume
- 16
- Issue
- 1
- Pages
- 8511-8511
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12474906
- OpenAlex
- W4414543818
- Cited by
- 26
- References
- 53
- Citations by year
- 2026: 20 · 2025: 5
- FWCI
- 17.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R01DK117425, R01HL135046, R01DK132211)
- National Science Foundation (EEC 1941543)
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › nanoparticles nucleation surface interactions
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- organ cryopreservation, organ banking, cryoprotectants, nanowarming, RF heating, convective cooling, critical cooling rate, porcine liver, iron oxide nanoparticles, M22, organ perfusion
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.
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