Making microencapsulation work: conformal coating, immobilization gels and in 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(hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA). Conformal coating was used to coat cell aggregates with a very thin layer of a water-insoluble HEMA-MMA membrane that conforms to the shape of the aggregate, and minimizes the polymer's contribution to the total transplant volume. Cell aggregates were coated at a liquid-liquid interface of a discontinuous density gradient composed of both aqueous and organic liquids. Aggregates of HepG2 cells were coated and remained viable. Immobilization matrices were co-encapsulated in order to control cell phenotype. Ultralow gelling temperature agarose promoted the proliferation of HEK293 cells, while the viability of transfected C2C12 cells was improved in microcapsules that contained Matrigel. Rat or human hepatoma cells in HEMA-MMA microcapsules lost viability within a week after implantation into an omental pouch in Wistar rats. The 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 aggressive tissue reaction or if the latter caused the cells to starve or otherwise die. On the other hand, intraperitoneal implantation of microcapsules containing L929 cells in 'syngeneic' C3H mice in a high-strength agarose gel resulted in maintenance of viability of approximately 50% of the encapsulated cells. While progress is being made on several fronts, this type of tissue engineering construct is still several years away from routine use in humans.
Sefton
M V
MV
Institute for Biomaterials and Biomedical Engineering and Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada. sefton@ecf.utoronto.ca
May
M H
MH
Lahooti
S
S
Babensee
J E
JE
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D018914:Cells, Immobilized; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005782:Gels; D006801:Humans; D007274:Injections, Intraperitoneal; D007515:Islets of Langerhans; D008768:Methylmethacrylates; D051379:Mice; D008809:Mice, Inbred C3H; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D011102:Polyhydroxyethyl Methacrylate; D051381:Rats; D017208:Rats, Wistar; D012685:Sepharose
D005079:Excipients; D005782:Gels; D008768:Methylmethacrylates; D011102:Polyhydroxyethyl Methacrylate; C040206:HTR composite; D012685:Sepharose