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Immunocamouflage of Red Blood Cells by means of Layer-by-Layer Self-Assembly Technique for Medical Transfusion

Posted on:2012-10-12Degree:Ph.DType:Thesis
University:McGill University (Canada)Candidate:Mansouri, SaniaFull Text:PDF
GTID:2451390008992681Subject:Engineering
Abstract/Summary:
Shortages in the blood supply have potential life-threatening consequences for patients requiring rapid and urgent blood transfusion. Different attempts described in the literature to produce universal blood have drawbacks and still induce the activation of the immune system. We report here new means of universal red blood cells (RBCs) production using the Layer-by-Layer (LbL) self-assembly technique for the deposition of chitosan-graft-phosphorylcholine (CH-PC), poly-L-lysine-graft-polyethylene glycol (PLL-PEG), hyaluronic acid (HA) and alginate (AL) onto functional and non-fixed RBCs. This idea was based on previous findings where fixed RBCs have been used as template for LbL multilayer assembly for the production of hollow capsules. The aim of this thesis, therefore, was to coat fresh and functional red blood cells (RBCs) with a multilayered polymeric shell.;The main goal of this thesis was to develop a multilayer shell on non-fixed and functional RBCs in suspension. The design in suspension involved, CH-PC, PLL-PEG and AL that were successfully assembled in a nano-organized shell on non-fixed RBCs through the electrostatic LbL self-assembly technique. The RBCs' shape, morphology were not affected by the polyelectrolytes multilayers build-up. The multilayered nanoshell succeeded in preventing anti-A, anti-B, anti-Lewis y and anti-CD44 antibodies interactions with their specific antigens on the RBC membrane. Moreover, the RBCs maintained their initial role after their coating which is to carry oxygen. This research has demonstrated that LbL assembly of polyelectrolytes can be used as means to induce immunocamouflage of RBC antigens. As a preliminary step toward the clinical application of such universal red blood cells, an in vivo study was conducted to evaluate the safety and integrity of coated mice RBCs. The coated mice RBCs survived in bloodstream and did not trigger the immune system. These results represent a significant step toward the potential use of the coated RBCs as a universal blood in medical transfusion.;The natural polyelectrolytes, CH-PC, HA, PLL-PEG and AL were successfully assembled in a well-designed multilayer system on non-fixed RBCs in a two-dimensional (2-D) model through the electrostatic LbL assembly technique. A systematic study of constructs formed by two pairs of oppositely charged biocompatible polyelectrolytes has been performed. By modulating the film composition and build-up conditions, such as incorporating the protein-repulsive polyelectrolyte PLL-PEG, adjusting the film thickness and the multilayer permeability, cell recognition by the anti-A antibody is prevented.
Keywords/Search Tags:Blood, Self-assembly technique, PLL-PEG, Rbcs, Means, Multilayer
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