High-frequency viscoelastic shear properties of vocal fold tissues: implications for vocal fold tissue engineering.

The biomechanical function of the vocal folds (VFs) depends on their viscoelastic properties. Many conditions can lead to VF scarring that compromises voice function and quality. To identify candidate replacement materials, the structure, composition, and mechanical properties of native tissues need to be understood at phonation frequencies.

Design and characterization of a dynamic vibrational culture system.

To engineer a functional vocal fold tissue, the mechanical environment of the native tissue needs to be emulated in vitro. We have created a dynamic culture system capable of generating vibratory stimulations at human phonation frequencies. The novel device is composed of a function generator, a power amplifier, an enclosed loudspeaker and a circumferentially-anchored silicone membrane.

Measurements of the effects of decellularization on viscoelastic properties of tissues in ovine, baboon, and human heart valves.

In the development of tissue-engineered heart valves based on allograft decellularized extracellular matrix scaffolds, the material properties of the implant should be ideally comparable to the native semilunar valves. This investigation of the viscoelastic properties of the three functional aortic/pulmonary valve tissues (leaflets, sinus wall, and great vessel wall) was undertaken to establish normative values for fresh samples of human valves and to compare these properties after various steps in creating scaffolds for subsequent bioreactor-based seeding protocols. Torsional wave methods were used to measure the viscoelastic properties.

Tunable mechanical stability and deformation response of a resilin-based elastomer.

Resilin, the highly elastomeric protein found in specialized compartments of most arthropods, possesses superior resilience and excellent high-frequency responsiveness. Enabled by biosynthetic strategies, we have designed and produced a modular, recombinant resilin-like polypeptide bearing both mechanically active and biologically active domains to create novel biomaterial microenvironments for engineering mechanically active tissues such as blood vessels, cardiovascular tissues, and vocal folds. Preliminary studies revealed that these recombinant materials exhibit promising mechanical properties and support the adhesion of NIH 3T3 fibroblasts.

Assembly Properties of an Alanine-Rich, Lysine-Containing Peptide and the Formation of Peptide/Polymer Hybrid Hydrogels.

We are interested in developing peptide/polymer hybrid hydrogels that are chemically diverse and structurally complex. Towards this end, an alanine-based peptide doped with charged lysines with a sequence of (AKA(3)KA)(2) (AK2) was selected from the crosslinking regions of the natural elastin. Pluronic(®) F127, known to self-assemble into defined micellar structures, was employed as the synthetic building blocks.

Effects of matrix composition, microstructure, and viscoelasticity on the behaviors of vocal fold fibroblasts cultured in three-dimensional hydrogel networks.

Vocal fold diseases and disorders are difficult to treat surgically or therapeutically. Tissue engineering offers an alternative strategy for the restoration of functional vocal folds. As a first step toward vocal fold tissue engineering, we investigated the responses of primary vocal fold fibroblasts (PVFFs) to two types of collagen and hyaluronic acid (HA)-based hydrogels that are compositionally similar, but structurally variable and mechanically different.

Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based Doubly Cross-Linked Networks.

We have created a new class of hyaluronic acid (HA)-based hydrogel materials with HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a secondary network. HA HGPs with an average diameter of ∼900 nm and narrow particle size distribution were synthesized using a refined reverse micelle polymerization technique. The average mesh size of the HGPs was estimated to be approximately 5.

Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration.

Vocal fold scarring disrupts the viscoelastic properties of the lamina propria that are critical for normal phonation. There is a clinical need for the development of advanced biomaterials that approximate the mechanical properties of the lamina propria for in vivo vocal fold regeneration. We have developed hyaluronic acid (HA)-based microgels and cross-linked microgel networks with tunable degradation and mechanical properties.