Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord
Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord
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DOI：
10.1016/s0142-9612(03)00503-9
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发表时间：
2004-04-01
期刊：
影响因子：
14
通讯作者：
Oudega, M
中科院分区：
文献类型：
--
作者：
Patist, CM;Mulder, MB;Oudega, M
研究了聚（D，L-乳酸）大孔导向支架（泡沫）与或不与脑源性神经营养因子（BDNF）的组织保留，神经元存活，轴突再生，和后肢的行为改善植入横断成年大鼠胸脊髓的影响。将泡沫包埋在含有酸性成纤维细胞生长因子的纤维蛋白胶中。一组动物仅接受含酸性成纤维细胞生长因子的纤维蛋白胶。该泡沫通过热诱导聚合物-溶剂相分离过程制备，并且含有通过微孔网络彼此连接的纵向取向的大孔。泡沫和纤维蛋白仅导致索植入物界面出现相似的神经胶质和炎症反应。仅在植入后4周和8周，与对照泡沫或纤维蛋白相比，使用BDNF泡沫时，靠近头侧但非尾侧脊髓-植入物界面的脊髓神经组织中的NeuN阳性细胞存活率高出20%。半薄塑料切片和电子显微镜显示，细胞和轴突更迅速地侵入BDNF泡沫比对照泡沫。此外，在植入后8周，BDNF泡沫包含的血管几乎是对照泡沫的两倍。在所有三种植入范例中，组织保留相似;移植后8周，头侧脊髓中约42%的组织保留，尾侧脊髓中约37%的组织保留。有髓和无髓轴突的数量很低，两种类型的泡沫之间没有差异。在仅纤维蛋白的移植物中发现更多的轴突。在任何植入物中均未发现5-羟色胺能轴突，并且没有轴突再生到尾侧脊髓中。所有组的后肢行为改善相似。这些发现表明，泡沫在受损的脊髓内耐受良好，并且BDNF的添加促进细胞存活和血管生成。然而，总体轴突再生反应较低。未来的研究应探索使用聚（D，L-乳酸）泡沫。有或没有轴突生长促进因子，接种雪旺细胞以增强轴突再生和髓鞘形成反应。(C)2003年由爱思唯尔有限公司出版
The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use Of poly(D,L-lactic acid) foams. with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response. (C) 2003 Published by Elsevier Ltd.