Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury

Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury
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DOI:
10.1016/j.actbio.2017.11.028
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发表时间:
2018-01-15
期刊:
影响因子:
9.7
通讯作者:
Novikov, Lev N.
Novikov, Lev N.
中科院分区:
工程技术1区
文献类型:
--
作者:
Novikova, Liudmila N.;Kolar, Mallappa K.;Novikov, Lev N.

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脊髓损伤(SCI)通常与瘢痕形成和空洞形成有关,因此桥接策略对于为轴突再生提供物理基质至关重要。在这项研究中,我们研究了由三亚甲基碳酸酯和c-己内酯(TC)含有聚对二氧环己酮微丝(PDO)与纵向槽再生成年大鼠脊髓损伤后的生物可降解导管的影响。体外研究表明,不同类型的细胞,包括星形胶质细胞,脑膜成纤维细胞,雪旺细胞和成年感觉背根神经节神经元可以在TC和PDO材料上生长。对于体内实验,在损伤后立即(急性SCI)或在初始手术后2-5个月(慢性SCI)将TC/PDO导管植入C3-C4颈段中的2-3 mm长的小腔中。在植入急性SCI后8周,许多5 HT阳性的下行中缝脊神经轴突和感觉CGRP阳性轴突再生通过管道,并经常与PDO微丝和迁移的宿主细胞。植入到慢性损伤的SCI诱导再生主要是感觉CGRP阳性轴突。虽然与SCI对照相比,导管对OX 42阳性小胶质细胞的密度没有影响,但GFAP阳性星形胶质细胞的活性降低。结果表明,TC/PDO导管可以支持急性和慢性SCI后的轴突再生,即使没有添加外源性胶质细胞或干细胞。(C)2017 Acta Materialia Inc.爱思唯尔有限公司出版
Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and c-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd.