Materials Science and Engineering Program, Texas A&M University, College Station, TX 77843-3122, USA.
Acta Biomater. 2011 Nov;7(11):3964-72. doi: 10.1016/j.actbio.2011.06.034. Epub 2011 Jun 25.
Poly(ethylene glycol) (PEG) hydrogels have recently begun to be studied for the treatment of scarred vocal fold lamina propria due, in part, to their tunable mechanical properties, resistance to fibroblast-mediated contraction, and ability to be polymerized in situ. However, pure PEG gels lack intrinsic biochemical signals to guide cell behavior and generally fail to mimic the frequency-dependent viscoelastic response critical to normal superficial lamina propria function. Recent results suggest that incorporation of viscoelastic bioactive substances, such as glycosaminoglycans (GAGs), into PEG networks may allow these gels to more closely approach the mechanical responses of normal vocal fold lamina propria while also stimulating desired vocal fold fibroblast behaviors. Although a number of vocal fold studies have examined the influence of hyaluronan (HA) on implant mechanics and vocal fold fibroblast responses, the effects of other GAG types have been relatively unexplored. This is significant, since recent studies have suggested that chondroitin sulfate C (CSC) and heparan sulfate (HS) are substantially altered in scarred lamina propria. The present study was therefore designed to evaluate the effects of CSC and HS incorporation on the mechanical response of PEG gels and vocal fold fibroblast behavior relative to HA. As with PEG-HA, the viscoelasticity of PEG-CSC and PEG-HS gels more closely approached that of the normal vocal fold lamina propria than pure PEG hydrogels. In addition, collagen I deposition and fibronectin production were significantly higher in CSC than in HA gels, and levels of the myofibroblast marker smooth muscle α-actin (SM α-actin) were greater in CSC and HS gels than in HA gels. Since collagen I, fibronectin, and SM α-actin are generally elevated in scarred lamina propria these results suggest that CSC and HS may be undesirable for vocal fold implants relative to HA. Investigation of various signaling intermediates indicated that alterations in NFκB-p50, NFκB-p65, or pERK1/2 levels may underlie the observed differences among the PEG-GAG gels.
聚乙二醇（PEG）水凝胶最近开始被研究用于治疗瘢痕性声带固有层，部分原因是其可调的机械性能、抵抗成纤维细胞介导的收缩的能力以及原位聚合的能力。然而，纯 PEG 凝胶缺乏内在的生化信号来指导细胞行为，通常无法模拟对正常浅层固有层功能至关重要的频率依赖性粘弹性响应。最近的研究结果表明，将粘弹性生物活性物质（如糖胺聚糖（GAG））掺入 PEG 网络中，可能使这些凝胶更接近正常声带固有层的机械响应，同时刺激所需的声带成纤维细胞行为。尽管许多声带研究都检查了透明质酸（HA）对植入物力学和声带成纤维细胞反应的影响，但其他 GAG 类型的影响相对较少。这很重要，因为最近的研究表明，硫酸软骨素 C（CSC）和硫酸乙酰肝素（HS）在瘢痕性固有层中发生了实质性改变。因此，本研究旨在评估 CSC 和 HS 掺入对 PEG 凝胶的机械响应和声带成纤维细胞行为的影响，相对于 HA。与 PEG-HA 一样，PEG-CSC 和 PEG-HS 凝胶的粘弹性更接近正常声带固有层，而不是纯 PEG 水凝胶。此外，CSC 凝胶中的胶原蛋白 I 沉积和纤维连接蛋白产生显著高于 HA 凝胶，CSC 和 HS 凝胶中的肌成纤维细胞标志物平滑肌α-肌动蛋白（SM α-actin）水平高于 HA 凝胶。由于胶原蛋白 I、纤维连接蛋白和 SM α-actin 通常在瘢痕性固有层中升高，这些结果表明，CSC 和 HS 相对于 HA 可能不适合声带植入物。对各种信号转导中间物的研究表明，NFκB-p50、NFκB-p65 或 pERK1/2 水平的改变可能是观察到的 PEG-GAG 凝胶之间差异的基础。
