BIOCOMPATIBILITY OF MANNURONIC ACID-RICH ALGINATES

Highly purified algin preparations free of adverse contaminants with e ndotoxins and other mitogens recently became available by a new purifi cation process (Klock et al., Appl, Microbiol. Biotechnol., 1994, 40, 638-643). An advantage of this purification protocol is that it can be applied to alginates with various ratios of mannuronic acid to guluro nic acid. High mannuronic acid alginate capsules are of particular pra ctical interest for cell transplantation and for biohybrid organs, bec ause mannuronate-rich alginates are usually less viscous, allowing one to make gels with a higher alginate content. This will increase their stability and reduce the diffusion permeability and could therefore p rotect immobilized cells more efficiently against the host immune syst em. Here we report the biocompatibility of purified, mannuronic acid-r ich alginate (68% mannuronate residues) in a series of in vitro, as we ll as in vivo, assays. In contrast to raw alginate extracts, the purif ied product showed no mitogenic activity towards murine lymphocytes in vitro. Its endotoxin content was reduced to the level of the solvent. Animal studies with these new, purified algin formulations revealed t he absence of a mitogen-induced foreign body reaction, even when the p urified material (after cross-linking with Ba2+ ions) is implanted int o animal models with elevated macrophage activity (diabetes-prone BB/O K rat). Thus, alginate capsules with high mannuronic acid content beco me available for applications such as implantation. In addition to the utilization as implantable cell reactors in therapy and biotechnology , these purified algins have broad application potential as ocular fil lings, tissue replacements, microencapsulated growth factors and/or in terleukins or slow-release dosage forms of antibodies, surface coating s of sensors and other invasive medical devices, and in encapsulation of genetically engineered cells for gene therapy. (C) 1997 Elsevier Sc ience Limited.