Munoz-Pinto Dany J, Jimenez-Vergara Andrea Carolina, Gelves L Marcela, McMahon Rebecca E, Guiza-Arguello Viviana, Hahn Mariah S
Department of Chemical Engineering, Texas A&M University, 200 Jack E Brown Bldg, 3122 TAMU, College Station, Texas 77843-3122, USA.
Biotechnol Bioeng. 2009 Nov 1;104(4):821-31. doi: 10.1002/bit.22436.
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.
目前正在对包括定制植入物在内的多种治疗声带瘢痕的方法进行研究。本研究的目的是验证一种三维模型系统，以探究各种生物活性部分对声带成纤维细胞（VFF）行为的影响，从而进行合理的植入物设计。由于聚（乙二醇）二丙烯酸酯（PEGDA）水凝胶具有广泛可调的材料特性，我们选择其作为基础支架。然而，由于封装在PEGDA水凝胶中的细胞通常被迫呈现圆形/星状形态，因此要将PEGDA凝胶验证为三维VFF模型系统，本研究需要直接与之前涉及更宽松支架的研究相平行。因此，我们选择专注于透明质酸（HA），这是一种在声带领域备受关注的多糖。为此，将猪VFF封装在含有一致水平的高Mw HA（HA(HMW)）、中等Mw HA（HA(IMW)）或对照多糖藻酸盐的PEGDA水凝胶中，并培养7天和21天。相对于HA(IMW)，HA(HMW)促进了活性ERK1/2的持续增加。此外，在第21天时，HA(IMW)凝胶中的VFF比HA(HMW)和藻酸盐凝胶中的VFF表现出更类似肌成纤维细胞的表型、更高的弹性蛋白产量和更高的蛋白激酶C（PkC）水平。本结果与之前一项关于VFF在允许细胞伸长的基于胶原蛋白的支架中对HA(IMW)相对于藻酸盐的反应的三维研究一致，表明PEGDA水凝胶可作为一种有效的三维模型系统，用于探究VFF行为的至少某些方面。
