Bryant Stephanie J, Nicodemus Garret D, Villanueva Idalis
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309-0424, USA.
Pharm Res. 2008 Oct;25(10):2379-86. doi: 10.1007/s11095-008-9619-y. Epub 2008 May 29.
Synthetic hydrogels fabricated from photopolymerization are attractive for tissue engineering for their controlled macroscopic properties, the ability to incorporate biological functionalities, and cell encapsulation. The goal of the present study was to exploit the attractive features of synthetic hydrogels to elucidate the role of gel structure and chemistry in regulating biomechanical cues.
Cartilage cells were encapsulated in poly(ethylene glycol) (PEG) hydrogels with different crosslinking densities. Cellular deformation was examined as a function of gel crosslinking. The effects of continuous versus intermittent dynamic loading regimens were examined. RGD, a cell adhesion peptide, was incorporated into PEG gels and subjected to mechanical loading. Chondrocyte morphology and activity was assessed by anabolic and catabolic ECM gene expression and matrix production by collagen and glycosaminoglycan production.
Cell deformation was mediated by gel crosslinking. In the absence of loading, anabolic activity was moderately upregulated while catabolic activity was significantly inhibited regardless of gel crosslinking. Dynamic loading enhanced anabolic activities, but continuous loading inhibited catabolic activity, while intermittent loading stimulated catabolic activity. RGD acted as a mechanoreceptor to influence tissue deposition.
We demonstrate the ability to regulate biomechanical cues through manipulations in the gel structure and chemistry and cartilage tissue engineering.
由光聚合制备的合成水凝胶因其可控的宏观性质、整合生物功能的能力以及细胞封装特性，在组织工程领域颇具吸引力。本研究的目的是利用合成水凝胶的这些吸引人的特性，阐明凝胶结构和化学性质在调节生物力学信号中的作用。
将软骨细胞封装在具有不同交联密度的聚乙二醇（PEG）水凝胶中。研究细胞变形作为凝胶交联的函数。考察了连续与间歇动态加载方案的影响。将细胞黏附肽RGD掺入PEG凝胶中并进行机械加载。通过合成代谢和分解代谢的细胞外基质基因表达以及胶原蛋白和糖胺聚糖的产生来评估软骨细胞的形态和活性。
细胞变形由凝胶交联介导。在无加载情况下，无论凝胶交联如何，合成代谢活性适度上调，而分解代谢活性显著受到抑制。动态加载增强了合成代谢活性，但连续加载抑制了分解代谢活性，而间歇加载刺激了分解代谢活性。RGD作为一种机械感受器影响组织沉积。
我们证明了通过对凝胶结构和化学性质进行操作以及在软骨组织工程中调节生物力学信号的能力。
