Chronic liver disease leading to cirrhosis is a leading cause of death in the United States. For patients suffering from end-stage hepatic failure the treatment option is organ transplantation. While hepatocyte transplantation offers a less intrusive alternative to liver replacement, the maintenance of hepatocytes in traditional primary culture includes many obstacles. Most cell culture studies using hepatocytes are performed using the standard 2D “sandwich” culture. Yet, results have shown that when cultured using this standard method, normal mature hepatocytes quickly lose functionality. A major focus in our lab has been to address this problem by developing methods to efficiently differentiate iPSC-derived hepatocytes to a mature hepatic state. Our lab has previously demonstrated increased functionality of both normal and iPSC-derived hepatocytes when cultured on 3D scaffolds derived from the natural liver extracellular matrix (ECM). However, a drawback of this technology is that it relies on the natural liver substrate which may be variable, and thus the reproducibility of this approach is limited. We hypothesize that the use of a synthetic scaffold that mimics the liver ECM will enhance hepatocyte function. Therefore, our current research focuses on the development and evaluation of synthetic 3D scaffolds for maintenance of viability and function of hepatocytes. Synthetic scaffolds composed of poly (lactic-co-glycolic acid) (PLGA) with extracellular matrix (ECM) proteins attached to the surface were successfully prepared using electrospinning technology. The PLGA-ECM scaffolds were then evaluated as 3D hepatocyte culture systems. The results from the studies will be presented herein.

Development and evaluation of synthetic 3D scaffolds for the maintenance of viability and function of hepatocytes

253rd National Meeting (2017)

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