Evaluation of early and late effects into the acute spinal cord injury of an injectable functionalized self-assembling scaffold.
Evaluation of early and late effects into the acute spinal cord injury of an injectable functionalized self-assembling scaffold.
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DOI：
10.1371/journal.pone.0019782
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Gelain F
中科院分区：
文献类型：
--
作者：
Cigognini D;Satta A;Colleoni B;Silva D;Donegà M;Antonini S;Gelain F
脊髓损伤（SCI）后发生的复杂的生理病理学事件使这种毁灭性的创伤仍然无法治愈。自组装肽（SAP）是一种纳米材料，在再生医学中显示出一些有吸引力的特性，因为它们模拟了细胞外基质（ECM）的结构，可再吸收，允许生物功能化，并且可以直接注射到病变中。在这项研究中，我们评估了RADA 16 - 4G-BMHP 1 SAP的假定神经再生特性，证明其增强体外神经干细胞的存活和分化。这种SAP（RADA 16-I）已经用骨髓归巢基序（BMHP 1）功能化，并通过插入4-甘氨酸间隔子来优化，所述4-甘氨酸间隔子改善支架稳定性和生物基序的暴露。我们在大鼠脊髓挫伤后立即注射支架，然后通过半定量RT-PCR和组织学分析来评估早期效应和晚期效应。使用Basso，Beattie，Bresnahan（BBB）试验评估8周内的运动恢复情况。基因表达分析显示，在损伤后7天，功能化SAP诱导GAP-43，营养因子和ECM重塑蛋白的普遍上调，而SCI后3天没有观察到显着的变化。组织学分析显示，SCI后8周，我们的支架增加了细胞浸润，基底膜沉积和轴突再生/发芽的囊肿内。此外，官能化的SAP显示出与周围神经组织相容并至少部分填充空腔。最后，SAP注射导致两个后肢的运动性能和前肢-后肢协调的统计学显着改善。总之，这些结果表明，RADA 16 - 4G-BMHP 1诱导了有利的修复过程，如基质重塑，并为神经组织向内生长提供了物理和营养支持。因此，这种生物材料，最终与细胞和生长因子相结合，可能构成一个有前途的仿生支架再生应用在受损的中枢神经系统。
The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually combined with cells and growth factors, may constitute a promising biomimetic scaffold for regenerative applications in the injured central nervous system.
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影响因子：
5.3
作者：
Beattie, MS;Bresnahan, JC;Young, W
通讯作者：
Young, W
影响因子：
14
作者：
Gupta, D;Tator, CH;Shoichet, MS
通讯作者：
Shoichet, MS
纳米神经编织：用于大脑修复和轴突再生以及视力功能恢复的肽纳米纤维支架
DOI：
10.1073/pnas.0600559103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Ellis-Behnke, RG;Liang, YX;Schneider, GE
通讯作者：
Schneider, GE
影响因子：
10.8
作者：
Gelain, Fabrizio;Unsworth, Larry D.;Zhang, Shuguang
通讯作者：
Zhang, Shuguang
影响因子：
3.7
作者：
Gelain F;Bottai D;Vescovi A;Zhang S
通讯作者：
Zhang S