Chahine Nadeen O, Albro Michael B, Lima Eric G, Wei Victoria I, Dubois Christopher R, Hung Clark T, Ateshian Gerard A
Biomechanics & Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York, USA.
Biophys J. 2009 Aug 19;97(4):968-75. doi: 10.1016/j.bpj.2009.05.047.
In functional tissue engineering, the application of dynamic loading has been shown to improve the mechanical properties of chondrocyte-seeded agarose hydrogels relative to unloaded free swelling controls. The goal of this study is to determine the effect of dynamic loading on the transport of nutrients in tissue-engineered constructs. To eliminate confounding effects, such as nutrient consumption in cell-laden disks, this study examines the response of solute transport due to loading using a model system of acellular agarose disks and dextran in phosphate-buffered saline (3 and 70 kDa). An examination of the passive diffusion response of dextran in agarose confirms the applicability of Fick's law of diffusion in describing the behavior of dextran. Under static loading, the application of compressive strain decreased the total interstitial volume available for the 70 kDa dextran, compared to free swelling. Dynamic loading significantly enhanced the rate of solute uptake into agarose disks, relative to static loading. Moreover, the steady-state concentration under dynamic loading was found to be significantly greater than under static loading, for larger-molecular-mass dextran (70 kDa). This experimental finding confirms recent theoretical predictions that mechanical pumping of a porous tissue may actively transport solutes into the disk against their concentration gradient. The results of this study support the hypothesis that the application of dynamic loading in the presence of growth factors of large molecular weight may result in both a mechanically and chemically stimulating environment for tissue growth.
在功能组织工程中,相对于未加载的自由膨胀对照物,动态加载的应用已显示出可改善接种软骨细胞的琼脂糖水凝胶的机械性能。本研究的目的是确定动态加载对组织工程构建体中营养物质运输的影响。为了消除诸如载细胞圆盘内营养物质消耗等混杂效应,本研究使用无细胞琼脂糖圆盘和磷酸盐缓冲盐水中的葡聚糖(3 kDa和70 kDa)模型系统来研究加载引起的溶质运输响应。对葡聚糖在琼脂糖中的被动扩散响应的研究证实了菲克扩散定律在描述葡聚糖行为方面的适用性。在静态加载下,与自由膨胀相比,施加压缩应变减少了70 kDa葡聚糖可利用的总间隙体积。相对于静态加载,动态加载显著提高了溶质进入琼脂糖圆盘的摄取速率。此外,对于较大分子量的葡聚糖(70 kDa),发现动态加载下的稳态浓度显著高于静态加载下的稳态浓度。这一实验发现证实了最近的理论预测,即多孔组织的机械泵浦作用可能会逆着溶质浓度梯度将溶质主动运输到圆盘中。本研究结果支持这样的假设,即在存在大分子量生长因子的情况下施加动态加载可能会为组织生长创造一个机械和化学刺激的环境。