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半月板的组织工程

Tissue engineering of the meniscus.

作者信息

Buma P, Ramrattan N N, van Tienen T G, Veth R P H

机构信息

Orthopaedic Research Laboratory, Department of Orthopaedics, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

出版信息

Biomaterials. 2004 Apr;25(9):1523-32. doi: 10.1016/s0142-9612(03)00499-x.

Abstract

Meniscus lesions are among the most frequent injuries in orthopaedic practice and they will inevitably lead to degeneration of the knee articular cartilage. The fibro-cartilage-like tissue of the meniscus is notorious for its limited regenerative capacity. Tissue engineering could offer new treatment modalities for repair of meniscus tears and eventually will enable the replacement of a whole meniscus by a tissue-engineered construct. Many questions remain to be answered before the final goal, a tissue-engineered meniscus is available for clinical implementation. These questions are related to the selection of an optimal cell type, the source of the cells, the need to use growth factor(s) and the type of scaffold that can be used for stimulation of differentiation of cells into tissues with optimal phenotypes. Particularly in a loaded, highly complex environment of the knee, optimal mechanical properties of such a scaffold seem to be of utmost importance. With respect to cells, autologous meniscus cells seems the optimal cell source for tissue engineering of meniscus tissue, but their availability is limited. Therefore research should be stimulated to investigate the suitability of other cell sources for the creation of meniscus tissue. Bone marrow stroma cells could be useful since it is well known that they can differentiate into bone and cartilage cells. With respect to growth factors, TGF-beta could be a suitable growth factor to stimulate cells into a fibroblastic phenotype but the problems of TGF-beta introduced into a joint environment should then be solved. Polyurethane scaffolds with optimal mechanical properties and with optimal interconnective macro-porosity have been shown to facilitate ingrowth and differentiation of tissue into fibro-cartilage. However, even these materials cannot prevent cartilage degeneration in animal models. Surface modification and/or seeding of cells into the scaffolds before implantation may offer a solution for this problem in the future.This review focuses on a number of specific questions; what is the status of the development of procedures for lesion healing and how far are we from replacing the entire meniscus by a (tissue-engineered) prosthesis. Subquestions related to the type of scaffold used are: is the degree of tissue ingrowth and differentiation related to the initial mechanical properties and if so, what is the influence of those properties on the subsequent remodelling of the tissue into fibro-cartilage; what is the ideal pore geometry and what is the optimal degradation period to allow biological remodelling of the tissue in the scaffold. Finally, we will finish with our latest results of the effect of tear reconstruction and the insertion of prostheses on articular cartilage degradation.

摘要

半月板损伤是骨科临床最常见的损伤之一,不可避免地会导致膝关节软骨退变。半月板的纤维软骨样组织再生能力有限,这是出了名的。组织工程可为半月板撕裂的修复提供新的治疗方式,并最终实现用组织工程构建体替换整个半月板。在最终目标——组织工程半月板可用于临床应用之前,仍有许多问题有待解答。这些问题涉及最佳细胞类型的选择、细胞来源、是否需要使用生长因子以及可用于刺激细胞分化为具有最佳表型的组织的支架类型。特别是在膝关节负荷大、高度复杂的环境中,这种支架的最佳力学性能似乎至关重要。关于细胞,自体半月板细胞似乎是半月板组织工程的最佳细胞来源,但它们的获取有限。因此,应鼓励开展研究,以探究其他细胞来源用于构建半月板组织的适用性。骨髓基质细胞可能有用,因为众所周知它们可分化为骨细胞和软骨细胞。关于生长因子,转化生长因子-β(TGF-β)可能是一种合适的生长因子,可刺激细胞形成成纤维细胞表型,但随后应解决将TGF-β引入关节环境所带来的问题。具有最佳力学性能和最佳相互连通大孔隙率的聚氨酯支架已被证明有助于组织向内生长并分化为纤维软骨。然而,即使是这些材料也无法在动物模型中防止软骨退变。植入前对支架进行表面改性和/或将细胞接种到支架中,可能会在未来为解决这个问题提供一种方法。本综述聚焦于一些具体问题:损伤愈合程序的发展现状如何,以及我们距离用(组织工程)假体替换整个半月板还有多远。与所用支架类型相关的子问题包括:组织向内生长和分化的程度是否与初始力学性能有关,如果有关,这些性能对随后组织重塑为纤维软骨有何影响;理想的孔隙几何形状是什么,以及允许支架内组织进行生物重塑的最佳降解期是多久。最后,我们将介绍撕裂重建和假体植入对关节软骨退变影响的最新研究结果。

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