Electrospun polyurethane and hydrogel composite scaffolds to study valve cell fibrotic response

Advanced tissue engineering scaffolds are needed to mimic the natural extracellular matrix (ECM) makeup and function. In this study, valve interstitial cells (VICs) were encapsulated in 3D in a composite scaffold made from... [ view full abstract ]

Advanced tissue engineering scaffolds are needed to mimic the natural extracellular matrix (ECM) makeup and function. In this study, valve interstitial cells (VICs) were encapsulated in 3D in a composite scaffold made from biodegradable electrospun polyurethane (BPUR) and poly(ethylene glycol) (PEG). The electrospun polyurethane portion imparted mechanical strength comparable to natural valve tissue, while the PEG provided a cell-friendly substrate in which VICs were seeded in 3D. The resultant BPUR/PEG composite scaffold was tuned to match the tensile modulus, anisotropy, and extensibility of native aortic valve tissue. Seeded VICs remodeled the PEG portion of the composite scaffold in a heterogeneous manner. In some areas of the composite scaffold, VICs demonstrated a pronounced fibrotic response, with high levels of cell proliferation, αSMA expression, and collagen secretion. In contrast, cells in other parts of the scaffold exhibited a quiescent phenotype with low levels of αSMA expression and ECM secretion. In order to gain insight into the variability observed in cell behavior, composite scaffolds were cultured in a bent state, with cells seeded on the outer curve of the bent scaffold in tension and cells seeded on the inside curve of the bent scaffold experiencing compression. VICs demonstrated pronounced differences depending which side of the scaffold they were seeded. VICs in tension exhibited a fibrotic response, while VICs in compression were a quiescent phenotype. These results suggest that VIC behavior can be modulated through specific mechanical stimuli and may provide a means to guide ECM secretion in tissue engineering scaffolds.