title: Probing vocal fold fibroblast response to hyaluronan in 3D contexts.
abstract: A number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high Mw HA (HA(HMW)), intermediate Mw HA (HA(IMW)), or the control polysaccharide, alginate, and cultured for 7 and 21 days. HA(HMW) promoted sustained increases in active ERK1/2 relative to HA(IMW). Furthermore, VFFs in HA(IMW) gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in HA(HMW) and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to HA(IMW) relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior.
authors.affiliation: Department of Chemical Engineering, Texas A&M University, 200 Jack E Brown Bldg, 3122 TAMU, College Station, Texas 77843-3122, USA.
authors.forename: Dany J
authors.initials: DJ
authors.lastname: Munoz-Pinto
authors.forename: Andrea Carolina
authors.initials: AC
authors.lastname: Jimenez-Vergara
authors.forename: L Marcela
authors.initials: LM
authors.lastname: Gelves
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: McMahon
authors.forename: Viviana
authors.initials: V
authors.lastname: Guiza-Arguello
authors.forename: Mariah S
authors.initials: MS
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001688:Biological Products / Q000378:metabolism*; D018929:Cell Culture Techniques; D004549:Elastin / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000378:metabolism*; D020100:Hydrogels; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013552:Swine; D014827:Vocal Cords / Q000166:cytology*
chemical_list: D001688:Biological Products; D020100:Hydrogels; D006820:Hyaluronic Acid; D004549:Elastin; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3