In Vivo engineering of the vocal fold ECM with injectable HA hydrogels-late effects on tissue repair and biomechanics in a rabbit model.
OBJECTIVE
To determine if the utilization of injectable chemically modified hyaluronan (HA) derivative at the time of intentional vocal fold resection may facilitate wound repair and preserve the unique viscoelastic properties of the extracellular matrix (ECM) and lamina propria 6 months after treatment.


METHODS
Prospective, controlled animal study.


METHODS
Twelve rabbit vocal folds were biopsied bilaterally, and the left side of vocal fold was treated with Extracel, an injectable, chemically modified HA derivative, and the right side of vocal fold was injected with saline as control at the time of resection. Animals were sacrificed 6 months after biopsy and injection. Outcomes measured include transcription levels for procollagen, fibronectin, fibromodulin, transforming growth factor beta one (TGF-β1), HA synthase, and hyaluronidase, and tissue biomechanics-viscosity and elasticity.


RESULTS
Extracel-treated vocal folds were found to have significantly less fibrosis than saline-treated controls. Extracel-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. Significantly decreased levels of fibronectin, fibromodulin, TGF-β1, procollagen I, and HA synthase were measured.


CONCLUSIONS
Prophylactic in vivo manipulation of the ECM with an injectable HA hydrogel appears to induce vocal fold tissue regeneration to yield improved tissue composition and biomechanical properties at 6 months.
Thibeault
Susan L
SL
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin Madison, Madison, Wisconsin, USA. sarah-klemuk@uiowa.edu
Klemuk
Sarah A
SA
Chen
Xia
X
Quinchia Johnson
Beatriz H
BH
D000818:Animals; D001696:Biomechanical Phenomena; D004548:Elasticity; D005109:Extracellular Matrix / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics; D000071235:Fibromodulin; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis; D014453:Glucuronosyltransferase / Q000235:genetics; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006821:Hyaluronoglucosaminidase / Q000235:genetics; D020100:Hydrogels; D015552:Injections, Intralesional; D007820:Laryngeal Mucosa / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D011347:Procollagen / Q000235:genetics; D011446:Prospective Studies; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012212:Rheology; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014783:Viscosity; D014827:Vocal Cords / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D020100:Hydrogels; D011347:Procollagen; D011509:Proteoglycans; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000071235:Fibromodulin; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase
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