Date of Award

8-2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Webb, Ken

Committee Member

Vyavahare , Narendra

Committee Member

Ramamurthi , Anand

Committee Member

Yao , Hai

Abstract

Voice is produced by the conversion of aerodynamic energy from exhalation to acoustical energy for voice production by the vocal folds (membranous connective tissue) located in the larynx. The quality of voice depends on the biomechanical properties of the multi-layered vocal fold tissue which derive from its extracellular matrix (ECM) organization and composition. The wound healing response to vocal fold injuries is characterized by scarring and subsequent dysphonia due to alterations in the biomechanical properties of the tissue.
The work presented here is motivated by the importance of voice in maintaining quality of life and the inability of current treatment techniques to restore long-term, normal phonatory voice following injury induced scarring. We hypothesize that vibration is the epigenetic stimulus regulating the unique extracellular matrix (ECM) composition of the human vocal fold tissue and that rapid restoration of the vibratory microenvironment using mechano-mimetic scaffolds will facilitate:- (a) inhibition of scarring and (b) stimulation of fibroblast regeneration of the normal vocal fold tissue architecture/ECM composition and thereby restore long-term, normal phonaory voice. Our objective was to create in situ photopolymerizable, degradable, mechano-mimetic hydrogels/semi-interpenetrating networks (semi-IPNs) which may be introduced into critical size vocal fold defects using minimally invasive methods.
Towards this end, we created hyaluronic acid (HA) based hydrogels and polyethylene glycol (PEG)-diacrylate based hydrogels/semi-IPNs, which were found to approximate the viscoelastic mechanical properties of the native human vocal mucosa (vibratory component) and the vocal ligament (strain component), respectively. Cell culture studies indicated that these hydrogel/semi-IPN materials supported cell spreading, cell proliferation, and ECM deposition throughout the 3-dimensional crosslinked network. In an attempt to assess the ability of the HA-based hydrogels to support human fibroblast formation of vocal mucosa-specific matrix in response to physiologically relevant high frequency vibration, fibroblast encapsulated hydrogels were subjected to 2 hrs of vibration per day using a custom built vibrational bioreactor. Our results indicated that the exposure of HA hydrogel-encapsulated fibroblasts to physiologically relevant high frequency vibration stimulated a pattern of gene expression and ECM synthesis (upregulation of GAGs, downregulation of fibrous matrix proteins) consistent with the composition of the human vocal mucosa. In the future, these HA-based hydrogels introduced into the human vocal mucosa during the acute phase of wound healing by minimally invasive methods may bring about regeneration of the native human vocal mucosa ECM composition and thereby restore normal phonation.

Share

COinS