Characterization of the vocal fold lamina propria towards voice restoration

During normal speech, human vocal folds sustain greater than 100 high impact collisions each second. When the pliability of this complex biomechanical system is reduced by scarring, voice quality may be compromised. Currently, little can be done to treat patients affected with voice loss or chronic voice impairment due to scarring. Because of the size of the patient population suffering from voice impairment secondary to scarring, alternate treatment methods are currently being actively investigated. An implant-based approach is one strategy for treating lamina propria scarring. To rationally design an implant material for this purpose, it is important to have a more complete understanding of lamina propria biochemistry and microstructure than is currently in literature. This dissertation presents the following critical insights into normal human lamina propria biochemical structure: 1.) quantitative analysis of collagen, elastin, hyaluronan, and proteoglycan presence; 2.) quantitative examination of the spatial distributions of collagen, elastin, and hyaluronan, and qualitative investigation of the spatial distributions of specific proteoglycan types; and 3.) assessment of total cellularity and spatial variations in extracellular matrix turnover. Similar analyses have been carried out on the vocal fold lamina propria of normal dog, pig, and ferret towards identifying an appropriate animal model for implant trials. Dissertation Supervisor: Robert S. Langer Title: Germeshausen Professor, Chemical & Biomedical Engineering

[1]  J. Sandy,et al.  Aggrecan in bovine tendon. , 1994, Matrix biology : journal of the International Society for Matrix Biology.

[2]  I. Titze,et al.  Biomechanical and Histologic Observations of Vocal Fold Fibrous Proteins , 2000, The Annals of otology, rhinology, and laryngology.

[3]  R. Iozzo Matrix proteoglycans: from molecular design to cellular function. , 1998, Annual review of biochemistry.

[4]  A. Poole Proteoglycans in health and disease: structures and functions. , 1986, The Biochemical journal.

[5]  Philip L. Kelton,et al.  Physiology, Biochemistry, and Molecular Biology of the Skin , 1993 .

[6]  S. Schwartz,et al.  Distinct rat aortic smooth muscle cells differ in versican/PG-M expression. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[7]  E. Hammond,et al.  Immunocytochemical Study of Proteoglycans in Vocal Folds , 1996, The Annals of otology, rhinology, and laryngology.

[8]  J. Couchman,et al.  Mapping by monoclonal antibody detection of glycosaminoglycans in connective tissues , 1984, Nature.

[9]  S. Gray,et al.  Age- and Gender-Related Collagen Distribution in Human Vocal Folds , 2000, The Annals of otology, rhinology, and laryngology.

[10]  J. Davidson,et al.  Modulation of transforming growth factor‐beta 1 stimulated elastin and collagen production and proliferation in porcine vascular smooth muscle cells and skin fibroblasts by basic fibroblast growth factor, transforming growth factor‐α, and insulin‐like growth factor‐I , 1993 .

[11]  J. Couchman,et al.  Basement membrane and interstitial proteoglycans produced by MDCK cells correspond to those expressed in the kidney cortex. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[12]  G. Miserocchi,et al.  Development of lung edema: interstitial fluid dynamics and molecular structure. , 2001, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[13]  D. Bless,et al.  Interstitial protein alterations in rabbit vocal fold with scar. , 2003, Journal of voice : official journal of the Voice Foundation.

[14]  S. Chakravarti Functions of lumican and fibromodulin: Lessons from knockout mice , 2002, Glycoconjugate Journal.

[15]  S. McGowan,et al.  Basic fibroblast growth factor decreases elastin production by neonatal rat lung fibroblasts. , 1994, American journal of respiratory cell and molecular biology.

[16]  J. R. Coleman,et al.  Comparative Histology and Vibration of the Vocal Folds: Implications for Experimental Studies in Microlaryngeal Surgery , 2000, The Laryngoscope.

[17]  T. Nagasaka,et al.  Production and immunohistochemical characterization of a monoclonal antibody raised to proteoglycan purified from a human yolk sac tumour , 1989, The Histochemical Journal.

[18]  D. Heinegård,et al.  Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon. , 1984, The Biochemical journal.

[19]  A. Schmidtchen,et al.  Patterns of uronosyl epimerization and 4-/6-O-sulphation in chondroitin/dermatan sulphate from decorin and biglycan of various bovine tissues. , 1994, Glycobiology.

[20]  A. Garg,et al.  Inseparable iduronic acid-containing proteoglycan PG(IdoA) preparations of human skin and post-burn scar tissues: evidence for elevated levels of PG(IdoA)-I in hypertrophic scar by N-terminal sequencing. , 1996, Carbohydrate research.

[21]  A. Ghahary,et al.  Chemical characterization and quantification of proteoglycans in human post-burn hypertrophic and mature scars. , 1996, Clinical science.

[22]  B. Caterson,et al.  Identification of a monoclonal antibody that specifically recognizes corneal and skeletal keratan sulfate. Monoclonal antibodies to cartilage proteoglycan. , 1983, The Journal of biological chemistry.

[23]  T. Nagasaka,et al.  Production and characterization of monoclonal antibody to dermatan sulfate proteoglycan. , 1988, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[24]  E. Ruoslahti,et al.  Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. , 1994, The Biochemical journal.

[25]  P. Heitz,et al.  Distribution of the large aggregating proteoglycan versican in adult human tissues. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[26]  Steven D. Gray,et al.  Instability of Extracellular Matrix Gene Expression in Primary Cell Culture of Fibroblasts from Human Vocal Fold Lamina Propria and Tracheal Scar , 2002, The Annals of otology, rhinology, and laryngology.

[27]  A. Theocharis,et al.  Altered content composition and structure of glycosaminoglycans and proteoglycans in gastric carcinoma. , 2003, The international journal of biochemistry & cell biology.

[28]  M. Hirano,et al.  Age-Related Changes of Collagenous Fibers in the Human Vocal Fold Mucosa , 2002, The Annals of otology, rhinology, and laryngology.

[29]  H. Kagan,et al.  Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2. , 1994, American journal of respiratory cell and molecular biology.