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In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury

机译:原位胶凝水凝胶,用于脊髓缺损的保形修复,以及脊髓损伤后BDNF的局部递送

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摘要

Permanent functional loss usually occurs after injury to the spinal cord. Currently, a clinical strategy to promote regeneration in the injured spinal cord does not exist. It has become evident that in order to promote regeneration, a growth permissive substrate at the injury site is critical. In this study, we report the utilization of an agarose scaffold that gels in situ, conformally filling an irregular, dorsal over-hemisection spinal cord defect in adult rats. Besides being growth permissive, the scaffolds also serve as carriers of trophic factors when embedded with BDNF releasing microtubules. We report that our thermo-reversible scaffolds are capable of supporting 3D neurite extension in vivo and are effective carriers of drug delivery vehicles for sustained local delivery of trophic factors. We demonstrate that BDNF encourages neurite growth into the scaffolds, and reduces further the minimal inflammatory response agarose gels generate in vivo as evidenced by quantitative analysis of the extent of NF-160 kDA positive neurons and axons, GFAP positive reactive astrocytes, and CS-56 positive chondroitin sulfate proteoglycan at the interface of the scaffold and host spinal cord. We suggest that these thermo-reversible scaffolds have great potential to serve as growth permissive 3D scaffolds, and to present neurotrophic factors and potentially anti-scar agents to the injury site and enhance regeneration after spinal cord injury. (c) 2005 Elsevier Ltd. All rights reserved.
机译:永久性功能丧失通常发生在脊髓损伤后。目前,尚不存在促进受损脊髓再生的临床策略。显而易见的是,为了促进再生,在损伤部位生长允许的基质是至关重要的。在这项研究中,我们报告了一种在原位凝胶化的琼脂糖支架的利用,共形填充了成年大鼠不规则的背侧半截断脊髓缺损。除了允许生长外,当嵌入BDNF释放微管时,支架还可以作为营养因子的载体。我们报告说,我们的热可逆支架能够在体内支持3D神经突延伸,并且是药物运输工具的有效载体,可以持续局部输送营养因子。我们证明BDNF可促进神经突生长进入支架,并进一步减少体内产生的最小炎症反应琼脂糖凝胶,这是通过定量分析NF-160 kDA阳性神经元和轴突,GFAP阳性反应性星形胶质细胞和CS-56的程度来证明的支架和宿主脊髓界面处的硫酸软骨素蛋白多糖呈阳性。我们建议这些热可逆支架具有巨大的潜力,可以用作允许生长的3D支架,并向损伤部位呈现神经营养因子和潜在的抗瘢痕因子,并增强脊髓损伤后的再生。 (c)2005 Elsevier Ltd.保留所有权利。

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