Alternative surfaces for microcarrier culture of animal cells.

As part of an effort to broaden the applicability and efficiency of microcarrier cell culture various alternative new microcarriers were synthesized. The microcarriers were compared as substrates for the growth of several types of cells and with respect to binding of proteins from the culture medium. Cross-linked dextran has been found to be the most suitable material for a microcarrier matrix and was used as the matrix for the new microcarriers. One type of microcarrier was synthesized so that the charges necessary for cell attachment were present only in the surface layer of the microcarrier in the form of N,N,N-trimethyl-2-hydroxyaminopropyl groups. The resulting microcarriers had a very low capacity to bind proteins from the culture medium (e.g. albumin and IgG) and such proteins could be removed from the cultures more efficiently than when using previous microcarriers. A new principle was used for the development of the other type of microcarrier. A surface layer of cross-linked denatured collagen provided the surface for growth of cells. These microcarriers provided a "natural" substrate for cell growth and allowed improved attachment and spreading of cells with epithelial morphology. Harvesting cells from these microcarriers with proteolytic enzymes was more efficient than with previous microcarriers. The two alternative microcarriers should result in improved process efficiency and have a potential value in the preparation of live vaccines.