Biocompatibility of a synthetic extracellular matrix on immortalized vocal fold fibroblasts in 3-D culture.
In order to promote wound repair and induce tissue regeneration, an engineered hyaluronan (HA) hydrogel - Carbylan GSX, which contains di(thiopropionyl) bishydrazide-modified hyaluronic acid, di(thiopropionyl) bishydrazide-modified gelatin and polyethylene glycol diacrylate - has been developed for extracellular matrix (ECM) defects of the superficial and middle layers of the lamina propria. The purpose of this study was to evaluate the biocompatibility of Carbylan GSX in a previously established immortalized human vocal fold fibroblast (hVFF) cell line prior to human clinical trials. Immortalized hVFF proliferation, viability, apoptosis and transcript analysis for both ECM constituents and inflammatory markers were measured for two-dimensional and three-dimensional (3-D) culture conditions. There were no significant differences in morphology, cell marker protein expression, proliferation, viability and apoptosis of hVFF cultured with Carbylan GSX compared to Matrigel, a commercial 3-D control, after 1 week. Gene expression levels for fibromodulin, transforming growth factor-beta1 and tumor necrosis factor-alpha were similar between Carbylan GSX and Matrigel. Fibronectin, hyaluronidase 1 and cyclooxygenase II expression levels were induced by Carbylan GSX, whereas interleukins 6 and 8, Col I and hyaluronic acid synthase 3 expression levels were decreased by Carbylan GSX. This investigation demonstrates that Carbylan GSX may serve as a natural biomaterial for tissue-engineering of human vocal folds.
Chen
Xia
X
Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin - Madison, 5136 WIMR, 1111 Highland Ave, Madison, WI 53705-2275, USA.
Thibeault
Susan L
SL
D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005780:Gelatin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D008422:Materials Testing / Q000379:methods*; D016133:Polymerase Chain Reaction; D014827:Vocal Cords / Q000166:cytology*; D055815:Young Adult
D001672:Biocompatible Materials; D015415:Biomarkers; C513409:carbylan-GSX; D005780:Gelatin; D006820:Hyaluronic Acid