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Tissue Engineering

Tissue engineering involves combining engineering and biology to create materials that restore function in damaged or diseased tissues. This topic is relevant to communication sciences and disorders because many groups are currently applying tissue engineering strategies to vocal fold regeneration and replacement. When a recent study described an engineered vocal fold capable of lifelike vibration and sound production, headlines in the popular press conveyed the impression that clinical application was imminent. Patients with severe and intractable dysphonia will naturally be curious about such reports. As health-care providers are central to the assessment and treatment of dysphonia, Speech–Language pathologists (SLPs) should expect to field questions about tissue engineering relevant to the vocal folds. If and when engineered biomaterials are used in human vocal folds, SLPs will be responsible for understanding engineered tissues in order to apply evidence-based practice to this new dimension of voice assessment and treatment. This article reviews the principles of tissue engineering, progress made in the vocal folds, challenges of translation to clinical practice, and possible future directions for clinical applications.

Motivation for Vocal Fold Tissue Engineering

The complex layered structure of the extracellular matrix (ECM) proteins in the vocal fold lamina propria is uniquely suited to the biomechanical demands of voice production. The ECM provides the mechanical strength, elasticity, and shock absorption to withstand the impact, tensile, and shear forces induced by 100–300 tissue collisions per second in conversation as well as longitudinal stretch and recoil during pitch variation. Vocal fold scar, characterized by increased stiffness of the lamina propria due to altered concentration and organization of ECM proteins, represents a persistent problem in laryngology. Clinically, reduced pliability of the lamina propria translates to impaired voice quality and function. Traditional injectable fillers such as autologous fat, calcium hydroxylapatite, and collagen can improve glottic closure when injected into the thyroarytenoid muscle but do not sufficiently improve lamina propria pliability to restore voice function. There is no medical, surgical, or behavioral treatment that can restore the native structure and function of the lamina propria in vocal fold scar. Such restoration of function requires reversing the scar phenotype by inducing native cells to produce and maintain a healthy lamina propria ECM. This is the goal of tissue engineering, which involves the manipulation of three intersecting components: scaffolds, cells, and growth factors.

Scaffolds

Three-dimensional bioengineered scaffolds are a key component of tissue engineering. Scaffolds must mimic the structural and mechanical properties of the native tissue, support cellular adhesion and other behaviors, and allow for transport of oxygen and nutrients to cells. Importantly, scaffold materials should not trigger an inflammatory immune response, which could lead to increased tissue damage and to serious health problems. Finally, scaffolds should degrade over time, allowing for (1) controlled delivery of cells, growth factors, and drugs to the surrounding tissue and (2) gradual replacement of the engineered scaffold with native ECM produced by the body.

Common scaffold fabrications include sponges, spun fibers, and hydrogels. Materials can include synthetic polymers, biologically derived proteins and polysaccharides, and combinations of these. Due to the mechanical properties of the native lamina propria, size of the vocal folds, and the risk of further scar with surgical implantation, injectable hydrogels have been the primary scaffold fabrication used in vocal fold tissue engineering. Hyaluronic acid, a glycosaminoglycan, is the most commonly used material in vocal fold lamina propria tissue engineering, as it is highly prevalent in native vocal fold lamina propria, providing shock absorption and lubrication and optimizing viscoelasticity for tissue vibration. Hyaluronic acid is degraded very quickly by the body, so it must be chemically modified for use in biomaterials. Other materials used in the vocal folds include collagen, fibrin, alginate, synthetic polymers, and elastin-like and resilin-like polypeptides. Another option is ECM derived from decellularized tissue—for example, bladder, small intestine, or vocal fold lamina propria of a different species. Progress in scaffolds for the vocal folds includes in vitro assessment of biomechanical properties and effects on cell survival and behavior and testing in animal models to assess immunogenicity and to compare the viscoelastic properties of the material with native tissue.

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