Electrospun elastomeric vocal fold constructs for the application of vocal fold tissue engineering.

摘要

Voice disorders affect up to 9% of the population, and can be caused by vocal fold scarring. They can reduce the ability of a person to participate in the workplace and can also cause depression in individuals. Vocal fold scarring changes the organization and composition of the lamina propria, and affects the biomechanical properties of the tissue. These changes cause an inability of the lamina propria to produce a normal mucosal wave during speech, resulting in hoarseness or complete voice loss. Currently there is a clinical need for treatment options for vocal fold scarring.;This work focuses on developing a novel, elastomeric electrospun biomaterial to be used as a model system to evaluate the response of immortalized human vocal fold fibroblast cells (HVFF) to scaffold architecture and to the presence of an elastin polypeptide. The scaffold was developed by electrospinning Tecoflex(TM). Electrospun scaffolds were successfully made with aligned and unaligned fibers, and they were characterized using scanning electron microscopy (SEM) and uniaxial tensile testing. The aligned scaffolds had initial elastic moduli of ~14 MPa and ~0.3 MPa in the preferred and cross-preferred direction respectively. The unaligned scaffolds had initial elastic moduli of ~5 MPa and ~0.6 MPa in the preferred and cross-preferred direction respectively. An elastin-like polypeptide (ELP) developed in the Woodhouse lab, ELP4, was successfully adsorbed onto the scaffolds to investigate the effect of ELP's on the HVFF cells. HVFF cells were seeded onto the scaffolds and their viability, proliferation, morphology, and gene expression were characterized. Over the culture period the cells remained viable, and showed signs of proliferation. The scaffold topography had a significant impact on the orientation of the cells, with very aligned cultures on the aligned scaffold, and randomly oriented cells on the unaligned scaffold. The scaffold alignment and the ELP4 coating impacted the extracellular matrix gene expression. The ELP4 coating, and the aligned scaffolds promoted elastin synthesis when tested on day 7, and may also reduce collagen-3 expression on day 3. These results signify that aligned electrospun scaffolds, as well as an ELP4 coating, may be promising to use in future biodegradable vocal fold constructs.