December 2023
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44 Reads
Cryobiology
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December 2023
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44 Reads
Cryobiology
December 2023
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23 Reads
Cryobiology
June 2023
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136 Reads
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7 Citations
Annals of Biomedical Engineering
Vitrification could enable long-term organ preservation, but only after loading high-concentration, potentially toxic cryoprotective agents (CPAs) by perfusion. In this paper, we combine a two-compartment Krogh cylinder model with a toxicity cost function to theoretically optimize the loading of CPA (VMP) in rat kidneys as a model system. First, based on kidney perfusion experiments, we systematically derived the parameters for a CPA transport loading model, including the following: Vb = 86.0% (ra = 3.86 μm), Lp = 1.5 × 10-14 m3/(N·s), ω = 7.0 × 10-13 mol/(N·s), σ = 0.10. Next, we measured the toxicity cost function model parameters as α = 3.12 and β = 9.39 × 10-6. Combining these models, we developed an improved kidney-loading protocol predicted to achieve vitrification while minimizing toxicity. The optimized protocol resulted in shorter exposure (25 min or 18.5% less) than the gold standard kidney-loading protocol for VMP, which had been developed based on decades of empirical practice. After testing both protocols on rat kidneys, we found comparable physical and biological outcomes. While we did not dramatically reduce toxicity, we did reduce the time. As our approach is now validated, it can be used on other organs lacking defined toxicity data to reduce CPA exposure time and provide a rapid path toward developing CPA perfusion protocols for other organs and CPAs.
June 2023
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426 Reads
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77 Citations
Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.
December 2022
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24 Reads
Cryobiology
December 2022
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16 Reads
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1 Citation
Cryobiology
December 2022
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14 Reads
Cryobiology
December 2022
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9 Reads
Cryobiology
December 2022
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30 Reads
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1 Citation
Cryobiology
November 2022
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163 Reads
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1 Citation
Annals of Biomedical Engineering
... 101 Several studies have demonstrated that the colloidal and thermal stability of MNPs in VS55 can be maintained though surface coating with resorcinol-formaldehyde resin or silica. [104][105][106][107] Additionally, surface modification with poly(ethylene glycol) has been shown to reduce cellular interactions and thus cytotoxicity. 106,107 Manuchehrabadi achieved nanowarming of porcine arteries and porcine aortic heart valve leaflet tissues using magnetic heating. ...
September 2024
Nano Letters
... 101 Several studies have demonstrated that the colloidal and thermal stability of MNPs in VS55 can be maintained though surface coating with resorcinol-formaldehyde resin or silica. [104][105][106][107] Additionally, surface modification with poly(ethylene glycol) has been shown to reduce cellular interactions and thus cytotoxicity. 106,107 Manuchehrabadi achieved nanowarming of porcine arteries and porcine aortic heart valve leaflet tissues using magnetic heating. ...
April 2024
Nano Letters
... Researchers have effectively used different combinations of these CPAs, particularly EG and DMSO, on a variety of tissues and cells, including amnion-derived MSCs [39], cord blood [40], and embryos [41]. High concentrations of CPAs are necessary for the equilibrium vitrification process, which can potentially be detrimental to cells [42]. Consequently, the vitrification freezing method often requires both careful preparation of the CPA mixture and the gradual injection of the CPA at lower temperatures to ensure maximum safety. ...
December 2023
Cryobiology
... 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), where we have shown successful vitrification at 3L. Higher concentrations of CPAs such as VS83 (83% w/w CPA) have even lower CCR and can be more easily vitrified but increase biological toxicity relative to the CPAs chosen here [34]. To remain at a lower concentration of CPA and still achieve vitrification at higher volumes without toxicity, future work can assess the impact of ice recrystallization inhibitors (IRIs), polymers (e.g., polyglycerol-PGL, polyvinyl alcohol-PVA, polyethylene glycol-PEG, x-1000, z-1000, etc.), or other novel cryoprotective agents [35,36]. ...
June 2023
Annals of Biomedical Engineering
... Specimens have to be stored below −130 °C to avoid devitrification. Functional cryopreservation by vitrification is an active field of basic research, and has been successfully applied to the rat kidney and liver [31,32]. Functional cryopreservation has not yet been demonstrated for the whole adult mammalian brain, let alone body [33][34][35][36][37][38][39][40]. ...
June 2023
... Therefore warming rate is an important consideration in combatting freezing damage (Gao and Critser, 2000;Waters et al., 2020). In particular, a sample that has undergone vitrification may be especially susceptible to ice recrystallization if the warming rate is too slow (Bojic et al., 2021;Zhan et al., 2022). ...
December 2022
Cryobiology
... Apoptosis results when electrical pulses that are administered to cancer cells provoke thermal damage to internal structures and cell membranes [4]; it is known as inhibition of Fractal Fract. 2025, 9,34 2 of 20 proliferation on biological cells [5]. Healthy cells that are in the surrounding media are less sensitive to applied electrical pulses, avoiding significant damage. ...
October 2022
... Specimens have to be stored below −130 °C to avoid devitrification. Functional cryopreservation by vitrification is an active field of basic research, and has been successfully applied to the rat kidney and liver [31,32]. Functional cryopreservation has not yet been demonstrated for the whole adult mammalian brain, let alone body [33][34][35][36][37][38][39][40]. ...
October 2022
Annals of Biomedical Engineering
... Islets of Langerhans are mini-organs, cryopreserved islets or islets that have been cultured for a longer period, are usually not suitable for islet transplantation 2,4-8 . Although a great progress has been made in the cryopreservation of human islets 8 , in vitro culture of human islets, which will subject islets to stress, is still a necessary and critical step in islet transplantation, so that the quality and quantity of donor islets can be evaluated, and it also provides additional time to get recipients ready for the operation. In vitro culture of islets will also allow researchers to study their function, to characterize the subtype of cells in human islets, and to study the function of pancreatic genes or subtypes of cells. ...
April 2022
Nature Medicine
... In recent years, studies on organ and tissue cryopreservation have highlighted the importance of proper cryoprotectant addition. Contemporary cryoprotectants, like M22, VMP and VS55, contain any combination of the most commonly used cryoprotecting agents, ethylene glycol (EG) and DMSO [27], which have been used extensively in cryoprotection of human oocytes and zygotes [28], ovarian tissue [29], rat and rabbit kidneys [30,31], mouse hearts [32], and lamb cartilage [33]. ...
December 2021
Cryobiology