Postmodification of alginate-based microspheres with polyelectrolytes (PEs) is commonly used in the cell encapsulation field to control microsphere stability and permeability. However, little is known about how different applied PEs shape the microsphere morphology and properties, particularly in vivo. Here, we addressed this question using model multicomponent alginate-based microcapsules postmodified with PEs of different charge and structure. We found that the postmodification can enhance or impair the mechanical resistance and biocompatibility of microcapsules implanted into a mouse model, with polycations surprisingly providing the best results. Confocal Raman microscopy and confocal laser scanning microscopy (CLSM) analyses revealed stable interpolyelectrolyte complex layers within the parent microcapsule, hindering the access of higher molar weight PEs into the microcapsule core. All microcapsules showed negative surface zeta potential, indicating that the postmodification PEs get hidden within the microcapsule membrane, which agrees with CLSM data. Human whole blood assay revealed complex behavior of microcapsules regarding their inflammatory and coagulation potential. Importantly, most of the postmodification PEs, including polycations, were found to be benign toward the encapsulated model cells.

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Centre of Molecular Inflammation Research Department of Clinical and Molecular Medicine Faculty of Medicine and Health Sciences Norwegian University of Science and Technology Prinsesse Kristinas gt 1 NO 7491 Trondheim Norway

Department for Biomaterials Research Polymer Institute of the Slovak Academy of Sciences Dúbravská cesta 9 845 41 Bratislava Slovakia

Department of Biophotonics International Laser Centre Slovak Centre of Scientific and Technical Information Ilkovičova 3 841 04 Bratislava Slovakia

Department of Proteomics Institute of Virology Biomedical Research Center of the Slovak Academy of Sciences Dúbravská cesta 9 845 05 Bratislava Slovakia

Department of Visceral Surgery and Transplantation University Hospital Zurich Raemistrasse 100 8091 Zurich Switzerland

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského nám 2 162 06 Prague 6 Czech Republic

National Institute of Rheumatic Diseases Nábrežie 1 Krasku 4 921 12 Piešt'any Slovakia

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