Donor liver shortage is a crucial global public health
problem
as whole-organ transplantation is the only definitive cure for liver
disease. Liver tissue engineering aims to reproduce or restore function
through in vitro tissue constructs, which may lead to alternative
treatments for active and chronic liver disease. The formulation of
a multifunctional scaffold that has the potential to mimic the complex
extracellular matrix (ECM) and their influence on cellular behavior,
are essential for culturing cells on a construct. The separate employment
of topographic or biological cues on a scaffold has both shown influences
on hepatocyte survival and growth. In this study, we investigate both
of these synergistic effects and developed a new procedure to directly
blend whole-organ vascular perfusion-decellularized rat liver ECM
(dECM) into electrospun fibers with tailored surface nanotopography.
Water contact angle, tensile test, and degradation studies were conducted
to analyze scaffold hydrophilicity, mechanical properties, and stability.
The results show that our novel hybrid scaffolds have enhanced hydrophilicity,
and the nanotopography retained its original form after hydrolytic
degradation for 14 days. Human hepatocytes (HepG2) were seeded to
analyze the scaffold biocompatibility. Cell viability and DNA quantification
imply steady cell proliferation over the culture period, with the
highest albumin secretion observed on the hybrid scaffold. Scanning
electron microscopy shows that cell morphology was distinctly different
on hybrid scaffolds compared to control groups, where HepG2 began
to form a monolayer toward the end of the culture period; meanwhile,
typical hepatic markers and ECM genes were also influenced, such as
an increasing trend of albumin appearing on the hybrid scaffolds.
Taken together, our findings provide a reproducible approach and utilization
of animal tissue-derived ECM and emphasize the synergism of topographical
stimuli and biochemical cues on electrospun scaffolds in liver tissue
engineering.