In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.
OBJECTIVE
A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix.


METHODS
We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity.


RESULTS
The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity.


CONCLUSIONS
Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.
Hansen
Jennifer K
JK
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, The University of Utah, Salt Lake City, UT 84132-2301, USA.
Thibeault
Susan L
SL
Walsh
Jennifer F
JF
Shu
Xiao Zheng
XZ
Prestwich
Glenn D
GD
D000818:Animals; D001696:Biomechanical Phenomena; D002921:Cicatrix / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000187:drug effects* / Q000502:physiology; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D020100:Hydrogels / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D011446:Prospective Studies; D011817:Rabbits; D012212:Rheology; D023822:Tissue Engineering; D016896:Treatment Outcome; D014827:Vocal Cords / Q000187:drug effects* / Q000502:physiology / Q000601:surgery; D014832:Voice Disorders / Q000209:etiology / Q000517:prevention & control; D014945:Wound Healing / Q000187:drug effects*
D020100:Hydrogels; D006820:Hyaluronic Acid