Making microencapsulation work: conformal coating, immobilization gels andin vivo performance

Microencapsulation of cells as a means of insulin or other protein delivery (for example, for gene therapy) has not yet realized its potential. Three aspects of this problem are illustrated with reference to the use of poly(h ydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA). Conformal coat ing was used to coat cell aggregates with a very thin layer of a water-inso luble HEMA-R IMA membrane that conforms to the shape of the aggregate, and minimizes the polymer's contribution to the total transplant volume. Cell a ggregates were coated at a liquid-liquid interface of a discontinuous densi ty gradient composed of both aqueous and organic liquids. Aggregates of Hep G2 cells were coated and remained viable. Immobilization matrices were co-e ncapsulated in order to control cell phenotype, Ultralow gelling temperatur e agarose promoted the proliferation of HEK293 cells, while the viability o f transfected C2C12 cells was improved in microcapsules that contained Matr igel(R). Rat or human hepatoma cells in HEMA-MMA microcapsules lost viabili ty within a week after implantation into an omental pouch in Wistar rats. T he loss of viability was attributed to the tissue reaction, although it is not clear if the cells lost their viability in vivo leading to the aggressi ve tissue reaction or if the latter caused the cells to starve or otherwise die. On the other hand, intraperitoneal implantation of microcapsules cont aining L929 cells in 'syngeneic' C3H mice in a high-strength agarose gel re sulted in maintenance of viability of similar to 50% of the encapsulated ce lls. While progress is being made on several fronts, this type of tissue en gineering construct is still several years away from routine use in humans. (C) 2000 Elsevier Science B.V, All rights reserved.