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Cell microencapsulation and subsequent transplantation of the microencapsulated cells require multidisciplinary approaches. Physical, chemical, biological, engineering, and medical expertise has to be combined. Several natural and synthetic polymeric materials and different technologies have been reported for the preparation of hydrogels, which are suitable to protect cells by microencapsulation. However, owing to the frequent lack of adequate characterization of the hydrogels and their components as well as incomplete description of the technology, many results of in vitro and in vivo studies appear contradictory or cannot reliably be reproduced. This review addresses the state of the art in cell microencapsulation with special focus on microencapsulated cells intended for xenotransplantation cell therapies. The choice of materials, the design and fabrication of the microspheres, as well as the conditions to be met during the cell microencapsulation process, are summarized and discussed prior to presenting research results of in vitro and in vivo studies. Overall, this review will serve to sensitize medically educated specialists for materials and technological aspects of cell microencapsulation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Two types of hydrogel microspheres have been developed. Fast ionotropic gelation of sodium alginate (Na-alg) in the presence of calcium ions was combined with slow covalent cross-linking of poly(ethylene glycol) (PEG) derivatives. For the first type, the fast obtainable Ca-alg hydrogel served as spherical matrix for the simultaneously occurring covalent cross-linking of multi-arm PEG derivative. A two-component interpenetrating network was formed in one step upon extruding the mixture of the two polymers into the gelation bath. For the second type, heterobifunctional PEG was grafted onto Na-alg prior to gelation. Upon extrusion of the polymer solution into the gelation bath, fast Ca-alg formation ensured the spherical shape and was accompanied by cross-linker-free covalent cross-linking of the PEG side chains. Thus, one-component hydrogel microspheres resulted. We present the physical properties of the hydrogel microspheres and demonstrate the feasibility of cell microencapsulation for both types of polymer networks. [ABSTRACT FROM AUTHOR]

Abstract: Poly(N,N-diethylacrylamide) microgels (diameter<1000nm) with narrow size distribution were synthesised by Surfactant-Free Emulsion Polymerisation at 70°C in aqueous solution using potassium persulphate as initiator. The gels were characterised in comparison to the corresponding poly(N-isopropylacrylamide) microgels. They showed reversible collapse upon thermo-stimulation with a critical temperature between 28 and 30°C, i.e. slightly below the critical temperature of the corresponding linear molecules. The average particle diameter as determined by electron microscopy decreased with increasing stirring rate adjusted during synthesis, although the effect was less straightforward for the poly(N,N-diethylacrylamide) microgels than for the poly(N-isopropylacrylamide) ones. In microgel preparations produced at the highest stirring speeds, the presence of small particles was observed, possibly a manifestation of residual ‘precursor particles’. A first characterisation of the biocompatibility of the gels was done by the WST-1 viability and the LDH cytotoxicity assays using the human breast cancer cell line MCF-7 (ATCC HTB-22) and a human T leukaemia cell line (Jurkat, ATCC TIB-125) as probes. No short-term effects (time span covered in the investigation <4h) of the microgels on cell viability could be observed when the cell were incubated with the gels at 37°C, i.e. above the critical temperature. At 22°C and for microgel concentrations above 1mg/mL some cytotoxicity was observed. In general the cytotoxicity was more pronounced for the poly(N-isopropylacrylamide) microgels than for the poly(N,N-diethylacrylamide) ones. [Copyright &y& Elsevier]