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利用半透膜和灌注调节组织工程软骨中深度依赖性特性:基质代谢与运输的连续模型

Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion: a continuum model of matrix metabolism and transport.

作者信息

Klein T J, Sah R L

机构信息

Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr., Mail Code 0412, La Jolla, CA 92093-0412, USA.

出版信息

Biomech Model Mechanobiol. 2007 Jan;6(1-2):21-32. doi: 10.1007/s10237-006-0045-y. Epub 2006 May 20.

DOI:10.1007/s10237-006-0045-y
PMID:16715317
Abstract

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue- engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

摘要

软骨组织的功能特性主要由细胞外基质中蛋白聚糖和胶原蛋白的含量、分布及组织方式决定。细胞外基质通过基质分子的代谢和运输在组织工程软骨构建物中积累,这些过程受物理和化学因素调节。在自由膨胀条件下用可自由渗透或高渗透膜培养的构建物呈现出软组织的对称表面区域。组织特性随距表面深度的变化提出了这样一种假说,即由边界条件介导的运输过程控制着此类构建物中蛋白聚糖的分布。扩展了一个连续介质模型(迪米科和萨赫,《多孔介质传输》,50:57 - 73,2003年)以测试膜渗透性和灌注对组织工程软骨中蛋白聚糖积累的影响。分析了几种实验配置下可溶性、结合型和降解型蛋白聚糖的浓度随时间、空间和无量纲参数的变化情况。模型结果表明,由无量纲参数描述的膜表面边界条件和灌注速率是蛋白聚糖积累模式的重要决定因素。进行灌注时,蛋白聚糖分布呈偏态,其大小根据基于流量的刺激水平而减小或增加。使用有或没有单向流动的半透膜可能会导致蛋白聚糖含量随深度增加的组织,类似于天然关节软骨。

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