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. 2014 Jan 9;7(1):275-286.
doi: 10.3390/ma7010275.

Alginate-Poly(ethylene glycol) Hybrid Microspheres for Primary Cell Microencapsulation

Redouan Mahou  1 , Raphael P H Meier  2 , Léo H Bühler  3 , Christine Wandrey  4
Affiliations

Alginate-Poly(ethylene glycol) Hybrid Microspheres for Primary Cell Microencapsulation

Redouan Mahou et al. Materials (Basel). .

Abstract

The progress of medical therapies, which rely on the transplantation of microencapsulated living cells, depends on the quality of the encapsulating material. Such material has to be biocompatible, and the microencapsulation process must be simple and not harm the cells. Alginate-poly(ethylene glycol) hybrid microspheres (alg-PEG-M) were produced by combining ionotropic gelation of sodium alginate (Na-alg) using calcium ions with covalent crosslinking of vinyl sulfone-terminated multi-arm poly(ethylene glycol) (PEG-VS). In a one-step microsphere formation process, fast ionotropic gelation yields spherical calcium alginate gel beads, which serve as a matrix for simultaneously but slowly occurring covalent cross-linking of the PEG-VS molecules. The feasibility of cell microencapsulation was studied using primary human foreskin fibroblasts (EDX cells) as a model. The use of cell culture media as polymer solvent, gelation bath, and storage medium did not negatively affect the alg-PEG-M properties. Microencapsulated EDX cells maintained their viability and proliferated. This study demonstrates the feasibility of primary cell microencapsulation within the novel microsphere type alg-PEG-M, serves as reference for future therapy development, and confirms the suitability of EDX cells as control model.

Keywords: alginate; biocompatibility; cell encapsulation; cell transplantation; hydrogel; microencapsulation; poly(ethylene glycol).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Alginate-poly(ethylene glycol) hybrid microspheres (alg-PEG-M) with an average diameter of 550 μm ± 5% SD. Scale bar: 400 μm.
Figure 2.
Figure 2.
Microsphere preparations with different concentrations of vinyl sulfone-terminated multi-arm poly(ethylene glycol) (PEG-VS) in 1.5% (w/v) sodium alginate (Na-alg) PEG-VS concentrations: (A) 0% (w/v); (B) 1.25% (w/v); (C) 5% (w/v) and (D) 10% (w/v). Upper row before liquefaction; lower row same batches after liquefaction with 200 mM Na-citrate for 3 days. Scale bars: 500 μm.
Figure 3.
Figure 3.
Mechanical resistance to compression up to 90% of the microsphere diameter of individual alg-PEG-M prepared with 0%–10% (w/v) PEG-VS (n = 30 ± SD).
Figure 4.
Figure 4.
Microphotographs of non-encapsulated (left panel) and microencapsulated primary human foreskin fibroblasts (EDX cells) (right panel), visualization of representative examples at different time points (in days) up to 20 days after microencapsulation. Top, light microscopy; bottom, viability staining of the same objects with fluorescein diacetate (green: living cells) and propidium iodide (red: dead cells). The average diameter of the microspheres was 550 μm. Scale bars: 100 μm.
Figure 5.
Figure 5.
Viability of microencapsulated EDX cells at various time points (days) up to 20 days after microencapsulation.
Figure 6.
Figure 6.
Proliferation of EDX cells 24 h after microencapsulation in alg-PEG-M. From left to right: green (EdU) shows proliferating cells; blue (Hoechst) shows all cells; Merge shows the overlay of EDU and Hoechst. Scale bars: 100 μm.
Scheme 1.
Scheme 1.
Chemical structures of 8-arm poly(ethylene glycol) (8-arm PEG-OH) and vinyl sulfone-terminated 8-arm PEG (PEG-8-20) obtained after modification of PEG-OH with a molar mass of 20 kg/mol.
See this image and copyright information in PMC

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