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Apatite nanoparticles strongly improve red blood cell cryopreservation by mediating trehalose delivery via enhanced membrane permeation

Stefanic, Martin and Ward, Kevin and Tawfik, Harvey and Seemann, Ralf and Baulin, Vladimir and Guo, Yachong and Fleury, Jean-Baptiste and Drouet, Christophe Apatite nanoparticles strongly improve red blood cell cryopreservation by mediating trehalose delivery via enhanced membrane permeation. (2017) Biomaterials, 140. 138-149. ISSN 0142-9612

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Official URL: https://doi.org/10.1016/j.biomaterials.2017.06.018


Cryopreservation of red blood cells (RBC) is an important method for maintaining an inventory of rare RBC units and managing special transfusion circumstances. Currently, in a clinical setting, glycerol is used as cryoprotectant against freezing damage. After thawing and before transfusion, glycerol must however be removed to avoid intravascular hemolysis, via a complex and time-consuming deglycerolization process which requires specialized equipment. Improved cryopreservation methods using non-toxic agents are required to increase biocompatibility and decrease processing time. Biocompatible cryoprotectants (e.g. trehalose) were proposed, but their low permeation through RBC membranes limits their cryoprotection efficacy. Herein, we report for the first time a glycerol-free cryopreservation approach, using colloidal bioinspired apatite nanoparticles (NP) as bioactive promoters of RBC cryopreservation mediated by trehalose. Addition of apatite NP in the medium tremendously increases RBC cryosurvival, up to 91% (42% improvement compared to a control without NP) which is comparable to FDA-approved cryoprotection protocol employing glycerol. NP concentration and incubation conditions strongly modulate the NP bioactivity. Complementary experimental and computational analyses of the interaction between apatite NP and model lipid bilayers revealed complex events occurring at the NP-bilayer interface. Apatite NP do not cross the bilayer but momentarily modulate its physical status. These changes affect the membrane behavior, and promote the permeation of trehalose and a model fluorescent molecule (FITC). This approach is a new alternative to using toxic glycerol for cells cryopreservation, and the identification of this enhancing no-pore permeation mechanism of apatite NP appears as an original delivery pathway for cryoprotectant agents and beyond.

Item Type:Article
HAL Id:hal-02401637
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:Other partners > Biopharma Group (UNITED KINGDOM)
French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > Universitat Rovira i Virgili (SPAIN)
Other partners > Institut "Jožef Stefan" - IJS (SLOVENIA)
Other partners > Universität des Saarlandes (GERMANY)
Laboratory name:
Marie Curie Actions - J.B. F.
Deposited On:10 Dec 2019 09:15

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