SURFACE MODIFICATION TO IMPROVE CELL ADHESION IN BIOREACTORS

SCIENTIFIC AND REGULATORY CONSIDERATIONS DICTATE THAT MANY VACCINES AND GENETICALLY ENGINEERED PROTEINS FOR USE IN IN HUMANS ARE BEST PRODUCED IN MAMMALIAN CELL LINES DERIVED FROM NON-MALIGNANT SOURCES. THESE CELLS USUALLY REQUIRE A SURFACE UPON WHICH TO GROW, AND SEVERAL BIOREACTOR CONFIGURATIONS HAVE BEEN DEVELOPED WHICH HAVE LARGE SURFACE AREAS COMPRESSED INTO SMALL VOLUMES, THEREBY IMPROVING THE EFFICIENCY OF THE SYSTEM. CURRENTLY, HOWEVER, THE INTERNAL SURFACES ARE NOT ADEQUATE FOR LONG-TERM CELL CULTURE; THE GREATEST PROBLEM IS THAT CELLS TYPICALLY DIE DETACH AFTER FOUR TO SIX WEEKS, THUS GREATLY LIMITING THE USEFUL LIFE OF SUCH BIOREACTORS. IN PHASE I, WE PROPOSETO COVALENTLY IMMOBILIZE NATURALLY OCCURRING CELL ADHESION PROTEINS ONTO SURFACES SUITABLE FOR LARGE-SCALE CELL CULTURE, AND THEN TEST THEIR EFFECTIVENESS IN IMPROVING INITIAL CELL ATTACHMENT, CELL GROWTH, AND LONG-TERM VIABILITY USING THREE REPRESENTATIVE CELL LINES. IN PHASE II, WE PROPOSE TO CONDUCT MORE EXTENSIVE LONG-TERM EVALUATIONS, TEST VARIOUS CELL LINES, AND INVESTIGATE CELL GROWTH IN SERUM-FREE MEDIA. PROOF-OF-CONCEPT OF THIS TECHNOLOGY SHOULD GREATLY IMPROVE THE USEFULNESS OF BIOREACTORS IN PRODUCING CERTAIN PROTEINS FOR PHARMACEUTICAL USE.