Very limited medical and surgical options are available for treating laryngeal pathologies characterized by tissue damage and deficiencies in the vocal fold lamina propria, largely due to the fact that an optimal, surgically implantable biomaterial for reconstruction and regeneration of the vocal fold lamina propria extracellular matrix (ECM) has yet to be developed. Such a material should have biomechanical properties and vibratory properties similar to those of the lamina propria ECM in order to facilitate functional phonatory performance of the vocal fold. It should also be able to promote new tissue formation and constructive remodeling as well as simulate the complex composition of the vocal fold ECM. In our previous studies, we developed a novel acellular, xenogeneic tissue engineering scaffold derived from bovine vocal fold lamina propria. Furthermore, we have successfully manufactured the ECM scaffold in a gel form which ensures its minimally invasive implantation. To further adjust the biomechanical and biochemical properties of the scaffold gel, we will test the concept of incorporating hyaluronic acid (HA) in the ECM scaffold gel to create a hybrid gel with tunable viscoelasticity and adjustable HA content. The goal of this project is to explore the potential of this novel injectable material (ECM-HA gel) for vocal fold lamina propria regeneration specifically in terms of the maintenance and restoration of normal viscoelasticity for functional vibratory performance. For the proposed funding period, we will first measure the viscoelasticity of the ECM-HA gel with different HA concentrations. Then in vivo and in vitro biocompatibility of the hybrid gels will be examined. We will determine the efficacy of the ECM-HA gel for the prevention of vocal fold scarring in vivo, when it is being implanted into the lamin propria immediately before induced vocal fold injury in a rabbit model. We will also explore the potential of the ECM-HA gel for the treatment of chronic vocal fold scarring, when it is implanted into the lamina propria six months after injury in the rabbit model. Quantitative methodologies will be used to compare the tissue compositions, viscoelastic properties, vibration patterns of the treated vocal fold at different time points to those of the contralateral untreated injured vocl fold. In the proposed studies, we will test the overall hypothesis that an injectable gel consistin of solubilized acellular vocal fold lamina propria extracellular matrix and hyaluronic acid can be used for surgical reconstruction of damaged vocal fold lamina propria in vivo.

Public Health Relevance

Each year, an estimated 3-9% of Americans suffer from some type of voice disorder, which adversely affects the communicative abilities, quality of life, and even the careers of individuals relying on a healthy, functional voice for their occupations. Recent advances in phonosurgical approaches and therapeutic strategies, vocal fold lamina propria defects, such as vocal fold scarring, atrophy and sulcus vocalis, remain among the most clinically challenging problems, due to the vulnerability of the vocal fold lamina propria to scar tissue formation and the difficulties in effectively replacing the lamina propria. The proposed research explores the concept of developing a new tissue engineering material by combining acellular biological ECM material with hyaluronic acid to facilitate the functional regeneration of the injured vocal fold lamina propria, which could lead to the development of effective surgical management for such voice disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Exploratory/Developmental Grants (R21)
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Motor Function, Speech and Rehabilitation Study Section (MFSR)
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Shekim, Lana O
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Xu, Chet C; Gao, Ang; Zhang, Song (2018) An investigation of left-right vocal fold symmetry in rheological and histological properties. Laryngoscope 128:E359-E364
Xu, Chet C; Chan, Roger W; Sun, Han et al. (2017) A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties. J Mech Behav Biomed Mater 75:477-485