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胶质神经导管的神经组织工程及不同细胞类型的影响

Neuro tissue engineering of glial nerve guides and the impact of different cell types.

作者信息

Lietz Martin, Dreesmann Lars, Hoss Martin, Oberhoffner Sven, Schlosshauer Burkhard

机构信息

NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstr. 55, D-72770 Reutlingen, Germany.

出版信息

Biomaterials. 2006 Mar;27(8):1425-36. doi: 10.1016/j.biomaterials.2005.08.007. Epub 2005 Sep 19.

Abstract

The aim of neuro tissue engineering is to imitate biological features in order to enhance regeneration. Following lesions of peripheral nerves, Schwann cells (SCs) reorganize to form longitudinal bands of Büngner (boB) which function as guides for regrowing axons. In order to imitate boB in synthetic implants designed to bridge nerve lesions, we developed resorbable, semipermeable nerve guide conduits with microstructured internal polymer filaments. We utilized a novel microcell chip and identified three extracellular matrix components conducive for coating non-permissive polymer surfaces. In order to maximize SC alignment, seven different microtopographies were investigated via the silicon chip technology. Special longitudinal microgrooves directed SC orientation and growing axons of dorsal root ganglia (DRG), thus achieving stereotropism. When these results were applied to microgrooved polymer filaments inside nerve guide conduits, we observed highly oriented axon growth without meandering. Since scar-forming fibroblasts could potentially interfere with axonal regrowth, triple cultures with fibroblasts, SC and DRG were conducted. Fibroblasts positioned on the outer nanopore containing conduit wall, did not hamper neuronal and glial differentiation inside the tube. In summary, for more rapid regrowth, functional boB can be induced by guided microtissue engineering. By considering both the negative and positive effects of cell interactions, a more rational design of nerve implants becomes feasible.

摘要

神经组织工程的目的是模仿生物特征以促进再生。外周神经损伤后,施万细胞(SCs)会重新组织形成Büngner纵束(boB),其作为轴突再生的引导。为了在用于桥接神经损伤的合成植入物中模仿boB,我们开发了具有微结构化内部聚合物细丝的可吸收、半透性神经引导导管。我们利用一种新型微细胞芯片,确定了三种有利于涂覆不支持性聚合物表面的细胞外基质成分。为了使SCs排列最大化,通过硅芯片技术研究了七种不同的微观形貌。特殊的纵向微槽引导SCs的方向以及背根神经节(DRG)轴突的生长,从而实现向心性生长。当将这些结果应用于神经引导导管内的微槽聚合物细丝时,我们观察到轴突高度定向生长且无迂曲。由于形成瘢痕的成纤维细胞可能会干扰轴突再生,因此进行了成纤维细胞、SCs和DRG的三重培养。位于含有纳米孔的导管外壁上的成纤维细胞不会妨碍管内神经元和神经胶质细胞的分化。总之,为了实现更快的再生,可以通过引导微组织工程诱导功能性boB。通过考虑细胞相互作用的正负效应,神经植入物的更合理设计变得可行。

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