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Functional tissue engineering of chondral and osteochondral constructs

机译:软骨和骨软骨构造的功能组织工程

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Due to the prevalence of osteoarthritis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, there is a great demand for an articular cartilage substitute. As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long-term culture environment, one can enhance the development of mechanical properties in chondrocyte-seeded agarose constructs. As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone. To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate. These osteochondral constructs develop cartilage-like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic deformational loading. The results of these models suggest that while chondral ("gel alone") constructs see a largely homogenous field of mechanical signals, osteochondral ("gel bone") constructs see a largely inhomogeneous distribution of mechanical signals. Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs. Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute.
机译:由于骨关节炎(OA)的流行和对关节软骨的损害,再加上这种无血管结缔组织的固有愈合能力差,因此对关节软骨替代物的需求很大。作为双关节关节的轴承材料,关节软骨具有显着的功能特性,这些特性很难在组织工程构造中复制。我们先前已经证明,通过使用一种将机械负荷结合到长期培养环境中的功能性组织工程方法,可以增强软骨细胞播种的琼脂糖构建体的机械性能。然而,随着这些凝胶构建体开始获得类似于天然组织的材料特性,出现了新的挑战,包括该构建体与下面的天然骨的整合。为了解决这个问题,我们开发了一种技术,用于生产整合到下面的骨基质中的凝胶构建体。这些骨软骨构建体在自由溶胀培养物中随时间发展软骨样细胞外基质和材料特性。在这项研究中,作为加载此类骨软骨构造的初步方法,有限元建模(FEM)用于预测承受动态变形载荷的构造中的时空应力,应变和流体流场。这些模型的结果表明,尽管软骨(“仅凝胶”)构建体看到了机械信号的大部分同质场,而骨软骨(“凝胶骨”)构建体看到了机械信号的大部分不均匀分布。机械环境中的这种不均匀性可能有助于工程骨软骨构造体中不均匀性的发展。连同实验观察结果,我们预计此类建模工作将为我们的工作提供方向,这些工作旨在优化骨软骨关节软骨替代物的功能组织工程的外加物理力。

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