The controlled presentation of TGF-β1 to hepatocytes in a 3D-microfluidic cell culture system

3D-microfluidic cell culture systems (3D-μFCCSs) support hepatocyte functions in vitro which can be further enhanced by controlled presentation of 100–200 pg/ml TGF-β1, thus mimicking the roles of supporting cells in co-cultures. Controlled presentation of TGF-β1 is achieved by either direct perfusion or in situ controlled release from gelatin microspheres immobilized in the 3D-μFCCS. Primary hepatocytes cultured for 7 days with the in situ controlled released TGF-β1 exhibited up to four-fold higher albumin secretion and two-fold higher phase I/II enzymatic activities, significantly improving the sensitivity of hepatocytes to acetaminophen-mediated hepatotoxicity, compared to hepatocytes cultured with directly perfused TGF-β1 or without TGF-β1. The controlled presentation of TGF-β1 enhanced hepatocyte functions in microfluidic systems without the complications of co-cultures, allowing for simplifications in drug testing and other hepatocyte-based applications.