Polyethylenimine Inclusion to Develop Aqueous Alginate-Based Core–Shell Capsules for Biomedical Applications

Aqueous core–shell structures can serve as an efficient approach that allows cells to generate 3D spheroids with in vivo-like cell-to-cell contacts. Here, a novel strategy for fabricating liquid-core–shell capsules is proposed by inverse gelation of alginate (ALG) and layer-by-layer (LbL) coating. We hypothesized that the unique properties of polyethylenimine (PEI) could be utilized to overcome the low structural stability and the limited cell recognition motifs of ALG. In the next step, alginate dialdehyde (ADA) enabled the Schiff-base reaction with free amine groups of PEI to reduce its possible toxic effects. Scanning electron microscopy and light microscopy images proved the formation of spherical hollow capsules with outer diameters of 3.0 ± 0.1 mm for ALG, 3.2 ± 0.1 mm for ALG/PEI, and 4.0 ± 0.2 mm for ALG/PEI/ADA capsules. The effective modulus increased by 3-fold and 5-fold when comparing ALG/PEI/ADA and ALG/PEI to ALG capsules, respectively. Moreover, PEI-coated capsules showed potential antibacterial properties against both Staphylococcus aureus and Escherichia coli, with an apparent inhibition zone. The cell viability results showed that all capsules were cytocompatible (above 75.5%). Cells could proliferate and form spheroids when encapsulated within the ALG/PEI/ADA capsules. Monitoring the spheroid thickness over 5 days of incubation indicated an increasing trend from 39.50 μm after 1 day to 66.86 μm after 5 days. The proposed encapsulation protocol represents a new in vitro platform for developing 3D cell cultivation and can be adapted to fulfill the requirements of various biomedical applications.