Core-Cross-Linked Alginate Microcapsules for Cell Encapsulation

Abstract

Self-cross-linkable polyelectrolyte pairs comprised of poly(methacrylic acid, sodium salt-co-2-[methacryloyloxy]ethyl acetoacetate) (70:30 mol ratio, A70) and poly-L-lysine are incorporated into CaAlg beads to form either a covalently cross-linked shell or a core-cross-linked bead. In both cases the reactive polyanion is added to a solution of sodium alginate that may contain live cells and dropped into a calcium chloride gelling bath. Subsequent exposure to poly-L-lysine (15-30 kDa) leads to formation of a cross-linked shell, while exposure to lower molecular weight poly-L-lysine (4-15 kDa) leads to formation of an interpenetrating matrix of covalently cross-linked synthetic polymer within the CaAlg template. The resulting spherical composites are resistant to chemical and mechanical stress yet remain cyto-compatible. This approach to cell-encapsulation may be useful for cell immuno-isolation in therapeutic cell transplants.

A review of bioactive plant polysaccharides: Biological activities, functionalization, and biomedical applications

“…A similar multilayer self-assembly approach by coating or depositing with oppositely charged polyelectrolytes bearing complementary amine and acetoacetate reactive groups has also been used to strengthen the alginate microcapsules by internally and externally cross-linked networks, which could become resistant to chemical and mechanical stress while remaining cyto-compatible. The resulting microcapsules are promising materials for cell encapsulation in cell-based therapies (Mazumder, Burke, Shen, Potter, & Stover, 2009;Mazumder, Shen, Burke, Potter, & Stover, 2008;. Moreover, multilayers could also be built from negatively charged alginate and positively charged chitosan in acid conditions and be used for cell adhesion in tissue engineering applications (Silva et al, 2013a).…”

Current status of hepatocyte xenotransplantation

“…Sodium alginate has a great biological acceptance and permeability upon ionotropic gelation with divalent cations [45,46], but it has the disadvantage of relatively low physical resistance and stability [47]. Variants of sodium alginate have been tested including barium alginate microbeads [48], ornithine alginate [49], carrageenan alginate [50], synthetic methacrylate-based polymers [51], poly-L-lysine [52], agarose [53], sodium cellulose sulfate [54] or poly(ethylene glycol) [55]. Poly(L-lysine) allows the design of microspheres with a layer that create a "real" capsule around cells rather than beads of sodium alginate that are solid compounds where cells are included.…”

Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment

“…However, ultrapure preparations have been described with improved capabilities [13,14] as well as alternate cross-linking methods that also improve the function of the capsules. [15] Nevertheless, clinical studies have been conducted without safety problems. Cellulose sulfate [sodium cellulose sulfate (NaCS)-polydimethyl-diallyl-ammonium chloride (PDMDAAC)], discovered more than 25 years ago, [16] on the other hand can be synthesized under controlled conditions but is difficult to handle since it is extremely difficult to dissolve.…”