Electrospun fiber constructs for vocal fold tissue engineering: Effects of alignment and elastomeric polypeptide coating

Abstract

Vocal fold lamina propria extracellular matrix (ECM) is highly aligned and when injured, becomes disorganized with loss of the tissue’s critical biomechanical properties. This study examines the effects of electrospun fiber scaffold architecture and elastin-like polypeptide (ELP4) coating on human vocal fold fibroblast (HVFF) behavior for applications toward tissue engineering the vocal fold lamina propria. Electrospun Tecoflex™ scaffolds were made with aligned and unaligned fibers, and were characterized using scanning electron microscopy and uniaxial tensile testing. ELP4 was successfully adsorbed onto the scaffolds; HVFF were seeded and their viability, proliferation, morphology, and gene expression were characterized. Aligned and unaligned scaffolds had initial elastic moduli of ~14 MPa, ~5 MPa and ~0.3 MPa, ~0.6 MPa in the preferred and cross-preferred directions, respectively. Scaffold topography had an effect on the orientation of the cells, with HVFF seeded on aligned scaffolds having a significantly different (p < 0.001) angle of orientation than HVFF cultured on unaligned scaffolds. This same effect and significant difference (p < 0.001) was seen on aligned and unaligned scaffolds coated with ELP4. Scaffold alignment and ELP4 coating impacted ECM gene expression. ELP4 coating, and aligned scaffolds upregulated elastin synthesis when tested on day 7 without a concomitant upregulation of collagen III synthesis. Collectively, results indicate that aligned electrospun scaffolds and ELP4 coating, are promising candidates in the development of biodegradeable vocal fold lamina propria constructs.

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

“…However, with the ELP4 coating, aligned fibrous scaffolds up-regulated elastin synthesis after 7 days of culturing without a concomitant up-regulation of collagen III synthesis. [154] Collectively, these results indicate that the elastin-coated, aligned scaffolds are promising candidates and could provide significant insights to guide vocal fold scar treatment.…”

“…[153] Inspired by the highly aligned and organized ECM network (which becomes disorganized upon injury) in normal vocal folds,[2,22] the Woodhouse and Thibeault groups investigated the impact of aligned and unaligned fibers on cellular morphology, gene expression, and matrix organization of vocal fold fibroblasts on electrospun, ELP4-coated TecoflexTM scaffolds for the development of potential VFLP construct candidates. [154] This ELP4 contains the VGCAPG-based 20-24-24-24-24 gene sequence with exon 21 and 23 as crosslinking domains between the hydrophobic domains. [155,156] The ELP4 coating was introduced to the electrospun scaffolds in order to enhance the biological function and promote ECM deposition during wound healing in scarred vocal fold tissues.…”

In Situ Generation of Cellulose Nanocrystals in Polycaprolactone Nanofibers: Effects on Crystallinity, Mechanical Strength, Biocompatibility, and Biomimetic Mineralization

“…11 The nanoscale fineness of electrospun biomaterials provides a structural extracellular matrix (ECM) network in which cells can grow during tissue repair and regeneration. 12 Therefore, electrospun nanofibrous membranes are widely used for tissue engineering including in complex tissues such as liver, bone, heart, and muscle. 13 To achieve these applications, electrospun nanofibrous mats should possess biodegradability, biocompatibility, and sufficient mechanical 4 strength.…”

Removal of retained electrospinning solvent prolongs drug release from electrospun PLLA fibers

“…Electrospun fibers are created for applications including filtration,[1–3] battery fabrication,[4–6] tissue engineering[7–11] and drug or protein delivery. [12–16] For cellular applications, electrospinning creates polymer nanofibers with diameters similar to those of fibrous proteins found in the extracellular matrix.…”