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进入凹槽:具有地形引导线索的指导性丝-聚吡咯膜引导背根神经节神经突生长。

Into the groove: instructive silk-polypyrrole films with topographical guidance cues direct DRG neurite outgrowth.

作者信息

Hardy John G, Khaing Zin Z, Xin Shangjing, Tien Lee W, Ghezzi Chiara E, Mouser David J, Sukhavasi Rushi C, Preda Rucsanda C, Gil Eun S, Kaplan David L, Schmidt Christine E

机构信息

a J. Crayton Pruitt Family Department of Biomedical Engineering , University of Florida , Gainesville , FL 32611 , USA.

b Department of Biomedical Engineering , The University of Texas at Austin , Austin , TX 78712 , USA.

出版信息

J Biomater Sci Polym Ed. 2015;26(17):1327-42. doi: 10.1080/09205063.2015.1090181. Epub 2015 Sep 28.

DOI:10.1080/09205063.2015.1090181
PMID:26414407
Abstract

Instructive biomaterials capable of controlling the behaviour of the cells are particularly interesting scaffolds for tissue engineering and regenerative medicine. Novel biomaterials are particularly important in societies with rapidly aging populations, where demand for organ/tissue donations is greater than their supply. Herein we describe the preparation of electrically conductive silk film-based nerve tissue scaffolds that are manufactured using all aqueous processing. Aqueous solutions of Bombyx mori silk were cast on flexible polydimethylsiloxane substrates with micrometer-scale grooves on their surfaces, allowed to dry, and annealed to impart β-sheets to the silk which assures that the materials are stable for further processing in water. The silk films were rendered conductive by generating an interpenetrating network of polypyrrole and polystyrenesulfonate in the silk matrix. Films were incubated in an aqueous solution of pyrrole (monomer), polystyrenesulfonate (dopant) and iron chloride (initiator), after which they were thoroughly washed to remove low molecular weight components (monomers, initiators, and oligomers) and dried, yielding conductive films with sheet resistances of 124 ± 23 kΩ square(-1). The micrometer-scale grooves that are present on the surface of the films are analogous to the natural topography in the extracellular matrix of various tissues (bone, muscle, nerve, skin) to which cells respond. Dorsal root ganglions (DRG) adhere to the films and the grooves in the surface of the films instruct the aligned growth of processes extending from the DRG. Such materials potentially enable the electrical stimulation (ES) of cells cultured on them, and future in vitro studies will focus on understanding the interplay between electrical and topographical cues on the behaviour of cells cultured on them.

摘要

能够控制细胞行为的指导性生物材料是组织工程和再生医学中特别有趣的支架。新型生物材料在人口快速老龄化的社会中尤为重要,在这些社会中,器官/组织捐赠的需求大于供应。在此,我们描述了基于导电丝膜的神经组织支架的制备,该支架采用全水性工艺制造。将家蚕丝的水溶液浇铸在表面具有微米级凹槽的柔性聚二甲基硅氧烷基体上,使其干燥并退火,以使丝具有β-折叠结构,这确保了材料在水中进一步加工时的稳定性。通过在丝基质中生成聚吡咯和聚苯乙烯磺酸盐的互穿网络,使丝膜具有导电性。将膜在吡咯(单体)、聚苯乙烯磺酸盐(掺杂剂)和氯化铁(引发剂)的水溶液中孵育,之后将其彻底洗涤以去除低分子量成分(单体、引发剂和低聚物)并干燥,得到方阻为124±23kΩ□⁻¹的导电膜。膜表面存在的微米级凹槽类似于各种组织(骨骼、肌肉、神经、皮肤)细胞外基质中的天然形貌,细胞会对其做出反应。背根神经节(DRG)附着在膜上,膜表面的凹槽引导从DRG延伸出的突起有序生长。这类材料有可能对培养在其上的细胞进行电刺激(ES),未来的体外研究将集中于了解电信号和形貌线索对培养在其上的细胞行为的相互作用。

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