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Stability of biodegradable microcarriers' surface: physically adsorbed versus chemically linked shells

Abstract

Mesenchymal Stem Cells (MSCs) are of increasing interest for tissue engineering and cellular therapy. MSCs expansion on microcarriers (MCs) in stirred bioreactor has emerged as an attractive method for their scale-up production. Some MCs have been developed based on polyesters as hydrophobic biodegradable core. However, most of these MCs are formulated with an emulsion/organic solvent evaporation (E/E) process using poly(vinyl alcohol) as shell steric stabilizer, which is biocompatible but not degradable in vivo. Moreover, for most of these MCs, the polymer shell is only physically adsorbed at the particle surface. To the best of our knowledge, no study deals with the stability of such shell when the MCs are in contact with competitive surfactant or with proteins contained in the culture medium. In this study, fully in vivo bioresorbable dextran-covered polylactide-based MCs were formulated using a E/E process, which allowed us to control their surface chemistry. Different dextran derivatives with alkyne or ammonium groups were firstly synthesised. Then, on the one hand, some MCs (non-clicked MCs) were formulated with a physically adsorbed polysaccharidic shell onto the core. On the other hand, the polysaccharidic shell was linked to the core via an in-situ CuAAC click-chemistry carried out during the E/E process (clicked MCs). The stability of such coverages was first studied in the presence of competitive surfactants (sodium dodecyl sulfate-SDS, or proteins contained in culture medium) using nanoparticles (NPs) exhibiting the same chemical composition (core/shell) than MCs. Results showed a total desorption of dextran shell for non-clicked NPs after treatment with SDS or the culture medium, while this shell desorption was greatly decreased for clicked NPs. Qualitative study of this shell stability was finaly carried out on MCs formulated using a new fluorescent dextran-based surfactant. Results were in agreement with those observed for NPs, and showed that non-clicked MCs are characterized by a poor shell stability in contact with a competitive surfactant, which could be quite an issue during MSCs expansion. On the contrary, clicked MCs possess a better shell stability, which allow a better control of the MCs surface chemistry, especially during cell culture.

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Publication details

The article was received on 11 May 2018, accepted on 11 Jul 2018 and first published on 12 Jul 2018


Article type: Paper
DOI: 10.1039/C8TB01255E
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Stability of biodegradable microcarriers' surface: physically adsorbed versus chemically linked shells

    A. Roy, M. A. MURCIA VALDERRAMA, V. Daujat, K. Ferji, M. Léonard, A. Durand, J. Babin and J. Six, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB01255E

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