To explore the scaffold's possible role in enhancing drug metabolism/clearance by the HepaRG hepatocytes, we chose drugs that 1) need to be metabolized by the liver before excretion, with limited direct excretion, 2) are well-studied and well-documented with abundant in vivo data available in the literature. The first drug tested was lidocaine 82 , a common anesthetic, which is mainly metabolized by CYP3A4 to monoethylglycinexylidide (MEGX), with less than 10% direct excretion (Figure ). The next drug we investigated was clozapine , an antipsychotic medication, which needs to be fully metabolized before excretion (Figure ). Clozapine is primarily metabolized by CYP1A2 and CYP3A4 to norclozapine. As with lidocaine, we observed faster clearance of the drug by the hepatocytes on dECM than on flat (Figure ). The error bars for the flat controls were large because we found the cells started to die with the clozapine, but not the cells on dECM, even with the same drug concentrations. As the key enzyme for fluoxetine metabolism (Figure ). These data highlight the necessity of including permeable excretion models to couple with liver models in future studies for efficient removal of metabolites, as occurs in vivo, for certain drug clearance studies.