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 baseβscaffold 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 M ~w~ HA (${\rm HA}_{{\rm H}{M}_{\rm W} } $), intermediate M~w~ HA (${\rm HA}_{{\rm I}{M}_{\rm W} } $), or the control polysaccharide, alginate, and cultured for 7 and 21 days. ${\rm HA}_{{\rm H}{M}_{\rm W} } $ promoted sustained increases in active ERK1/2 relative to ${\rm HA}_{{\rm I}{M}_{\rm W} } $ . Furthermore, VFFs in ${\rm HA}_{{\rm I}{M}_{\rm W} } $ gels displayed a more myofibroblastβlike phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in ${\rm HA}_{{\rm H}{M}_{\rm W} } $ and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to ${\rm HA}_{{\rm I}{M}_{\rm W} } $ relative to alginate in collagenβbased 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. Biotechnol. Bioeng. 2009; 104: 821β831 Β© 2009 Wiley Periodicals, Inc.