BIOCOMPATIBLE MEMBRANES FOR LONG-TERM IMPLANTATION IN THE STOMACH

ALTHOUGH MICRODIALYSIS HAS BEEN VERY USEFUL FOR THE ACUTE MONITORING OF THE BIOCHEMICAL MECHANISMS OF THE STOMACH AND ALIMENTARY TRACT, CHRONIC STUDIES HAVE NOT BEEN AS SUCCESSFUL. HOLLOW-FIBER MEMBRANES (HFMS) IMPLANTED FOR EXTENDED PERIODS IN THE STOMACH WALLS OF LABORATORY ANIMALS HAVE CAUSED INTENSE INFLAMMATORY RESPONSES WITHIN THE HOST TISSUE, AND OCCLUSION OF THE HFMS HAS RESULTED. IN ADDITION, MICRODIALYSIS FOR GASTROINTESTINAL APPLICATIONS HAS BEEN LIMITED DUE TO LOW RECOVERIES OF HIGHER MOLECULAR-WEIGHT COMPOUNDS SUCH AS NEUROPEPTIDES. THIS RESEARCH WILL INVESTIGATE BOTH OF THESE PROBLEMS IN AN EFFORT TO MAKE MICRODIALYSIS A MORE RELIABLE AND GLOBALLY APPLICABLE TECHNIQUE. DURING PHASE I RESEARCH, HFMS WILL BE MODIFIED USING BOTH LOW-TEMPERATURE PLASMA AND WET CHEMICAL SURFACE MODIFICATIONTECHNIQUES. MODIFIED FIBERS WILL BE IMPLANTED IN THE STOMACH WALLS OF RATS, AND THE EFFECT UPON THE SURROUNDING TISSUE AS WELL AS THE DIALYSIS RECOVERIES WILL BE MONITORED. IN ADDITION, PHYSICAL MODIFICATIONS TO THE HFM WILL BE INVESTIGATED FOR IMPROVEMENT OF RECOVERIES FOR HIGHER MOLECULAR-WEIGHT SPECIES. THESE EXPERIMENTS WILL LAY THE GROUNDWORK FOR LONG-TERM PHASE II STUDIES ON GASTRIC PEPTIDES FOUND IN EXTREMELY LOW IN VIVO CONCENTRATIONS.