Enzymatically fabricated and degradable microcapsules for production of multicellular spheroids with well-defined diameters of less than 150 microm.

Microcapsules with a single, spherical hollow core less than 150 microm in diameter were developed to obtain multicellular spheroids with well-defined sizes of less than 150 microm in diameter. An aqueous solution of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) containing human hepatoma cell line (HepG2) cells and horse radish peroxidase (HRP) was injected into a coflowing stream of liquid paraffin, containing H(2)O(2), resulting in cell-enclosing CMC-Ph microparticles, 135 microm in diameter, via a peroxidase-catalyzed crosslinking reaction. The CMC-Ph microparticles were then coated with a phenolic hydroxyl derivative of alginate (Alg-Ph) gel membrane several dozen micrometers in thickness, crosslinked via the same enzymatic reaction process, followed by further crosslinking between the carboxyl groups of alginate by Sr(2+).