核心技術

This study investigates the development of membranes for leukocytes depletion from model hydrogel interfaces. We first designed hydrogels from 2-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) to form poly(DMAEMA-co-PEGMA), and [2-(methacryloyloxy)ethyl] trimethylammonium chloride (TMA) and PEGMA to form poly(TMA-co-PEGMA). After characterizing the actual chemical composition of the hydrogels by XPS, efforts were made on studying the effect of the nature and content of amine functional group on the hydrophilicity and the surface charge of the gels. The adhesion of fibrinogen and blood cells was then methodically studied. Both types of gel are positively charged at pH 7.4, promoting fibrinogen and cell attachment. However, for the particular composition of 64% of DMAEMA in the hydrogel, results reveal that the adhesion of leukocytes was more important than that of erythrocytes and thrombocytes, thus suggesting that the control of the surface charge could lead to the selective adhesion of leukocytes. Based on these results, membranes were developed and tested in blood filtration for leukocyte depletion. Results prove that polypropylene membranes modified with a poly(DMAEMA-co-PEGMA) layer, containing 64% of DMAEMA can effectively lead to leukocyte depletion during blood filtration (99.6%) still maintaining a high erythrocytes recovery (98%).

Although widely used in blood-contacting devices, polypropylene (PP) membranes are prone to biofouling by plasma proteins and blood cells. The present study explores the effect of a surface zwitterionization process on the improvement of the biofouling resistance of PP membranes for leukocyte reduction filters. The modification strategy consists in forming an interpenetrating network of poly(glycidyl methacrylate-co-sulfobetaine metha- crylate) (poly(GMA-co-SBMA) around the fibers of coated PP membranes, using a cross-linking agent: ethyle- nediamine (EDA). It is shown that with EDA, a range of poly(GMA-co-SBMA) concentration (1–5 mg/mL) leads to a 0°-water contact angle and high hydration of the networks without affecting the intrinsic porous structure of the material. Besides, the related membranes show excellent resistance to biofouling by Escherichia coli, fi- brinogen, leukocytes, erythrocytes, thrombocytes and cells from whole blood with reductions in adsorption of 97%, 86%, 90%, 95%, 97% and 91%, respectively, compared to unmodified PP. Used in whole blood filtration, it is demonstrated that in the best conditions (5 mg/mL copolymer, with EDA), leukocytes can be efficiently re- moved (> 99.99%) without altering the erythrocytes concentration in the permeate, and that leukodepletion is more efficient than that measured with a commercial hydrophilic PP blood filter (about 50% retention). Physical retention of leukocytes is only efficient if the membrane material is anti-biofouling, and so, does not interact with other blood components able to trigger leukocyte attachment/deformation.

This chapter presents current efforts to design smart materials for blood separation, which do not rely on molecular sieving only, but on mechanisms of interactions between the membrane and the blood component to isolate. Although concepts have been introduced, there is more to do than has ever been done on this topic. This chapter stresses the need for a specific combination of materials to separate the component of interest from the bloodstream without inducing blood coagulation. PEGylated, zwitterionic and pseudo-zwitterionic materials can all improve the hemocompatibility of the membrane design. But to perform a smart separation, a charge bias has to be introduced by incorporating charged polymers, or a stimuli-responsive polymer has to be grafted which interactions with the blood component are tuned by environmental conditions. Attention is also given to methods for preparing supporting layers, poly(vinylidene fluoride)-based or polypropylene-based. Finally, examples of reported smart blood separations are scrutinized, including the separation of proteins from whole blood, the development of leukocyte depletion or platelet concentration filters. We end this chapter with an identification of the current challenges to overcome to expand the development of smart membranes for blood separation.