An exponential increase in liver disease is driving a critical shortage of donor livers for patient transplant. In the UK alone, 58 people died in 2019 while waiting for a donor organ. A solution is sought in the form of tissue-engineered devices which support the survival and function of primary human hepatocytes. Previous work has shown that biofunctionalization of electrospun scaffolds influences hepatocytes. This study assesses the impact of drug-derived ECM on primary human hepatocytes (PHHs); a gold standard research resource.
Hepatocytes seeded onto electrospun PLA scaffolds were subjected to drug treatment using histone deacetylase inhibitors. These cells were stripped from the scaffolds to leave behind their ECM. The resulting ECM-PLA scaffolds were seeded with PHHs and cultured for 24/72/120 hours. Scanning electron microscopy (SEM), mechanical and biochemical quantification, histology, and gene expression analyses were performed on the scaffolds.
Results demonstrate PHHs are significantly influenced by the drug derived ECM:PLA scaffolds, with alterations in albumin production and gene expression demonstrated.
Creating multidimensional scaffolds like these provides a method of creating tailored environments for liver bioengineering and the investigation of cell matrix interactions and is a step on the path to providing lab grown organoids for patient transplant.