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Vascularization of self-assembled peptide scaffolds for spinal cord injury repair.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.actbio.2019.12.033
Kiet A Tran 1 , Paul P Partyka 1 , Ying Jin 2 , Julien Bouyer 2 , Itzhak Fischer 2 , Peter A Galie 1
Affiliation  

The disruption of the blood-spinal cord barrier (BSCB) following spinal cord injury contributes to inflammation and glial scarring that inhibits axon growth and diminishes the effectiveness of conduits transplanted to the injury site to promote this growth. The purpose of this study is to evaluate whether scaffolds containing microvessels that exhibit BSCB integrity reduce inflammation and scar formation at the injury site and lead to increased axon growth. For these studies, a self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunocytochemistry and permeability transport assays verify the formation of tight-junction containing microvessels within the scaffold. Peptide scaffolds seeded with different concentrations of microvascular cells are then injected into a spinal contusion injury in rats to evaluate how microvessels affect axon growth and neurovascular interaction. The effect of the vascularized scaffold on inflammation and scar formation is evaluated by quantifying histological sections stained with ED-1 and GFAP, respectively. Our results indicate that the peptide scaffolds containing microvessels reduce inflammation and glial scar formation and increase the density of axons growing into the injury/transplant site. These results demonstrate the potential benefit of scaffold vascularization to treat spinal cord injury. STATEMENT OF SIGNIFICANCE: This study evaluates the benefit of transplanting microvascular cells within a self-assembling peptide scaffold, RADA-16I, that has shown promise for facilitating regeneration in the central nervous system in previous studies. Our results indicate that vasculature featuring tight junctions that give rise to the blood-spinal cord barrier can be formed within the peptide scaffold both in vitro and in a rat model of a subacute contusion spinal cord injury. Histological analysis indicates that the presence of the microvessels encourages axon infiltration into the site of injury and reduces the area of astrocyte activation and inflammation. Overall, these results demonstrate the potential of vascularizing scaffolds for the repair of spinal cord injury.

中文翻译:

自组装肽支架的血管化修复脊髓损伤。

脊髓损伤后血脊髓屏障(BSCB)的破坏导致炎症和神经胶质瘢痕形成,从而抑制轴突生长并削弱了移植到损伤部位的导管促进该生长的有效性。这项研究的目的是评估包含具有BSCB完整性的微血管的支架是否可以减少损伤部位的炎症和疤痕形成并导致轴突生长增加。在这些研究中,使用自组装肽支架RADA-16I,因为它具有对轴突生长的宽容性和支持血管生成的能力。免疫细胞化学和通透性转运测定法验证了支架内包含紧密连接的微血管的形成。然后将接种有不同浓度微血管细胞的肽支架注入大鼠脊髓挫伤中,以评估微血管如何影响轴突生长和神经血管相互作用。通过量化分别用ED-1和GFAP染色的组织切片来评估血管化支架对炎症和疤痕形成的作用。我们的结果表明,含有微血管的肽支架减少了炎症和神经胶质疤痕的形成,并增加了进入损伤/移植部位的轴突的密度。这些结果证明了支架血管化治疗脊髓损伤的潜在益处。重要性声明:这项研究评估了将微血管细胞移植到自组装肽支架RADA-16I中的益处,在先前的研究中已经显示出促进中枢神经系统再生的希望。我们的结果表明,在体外和在亚急性挫伤性脊髓损伤的大鼠模型中,可在肽支架内形成具有紧密连接并引起血脊髓屏障的血管系统。组织学分析表明,微血管的存在促进轴突渗透到损伤部位,并减少星形胶质细胞活化和炎症的面积。总的来说,这些结果表明血管支架在修复脊髓损伤中的潜力。我们的结果表明,在体外和在亚急性挫伤性脊髓损伤的大鼠模型中,可在肽支架内形成具有紧密连接并引起血脊髓屏障的血管系统。组织学分析表明,微血管的存在促进轴突渗透到损伤部位,并减少星形胶质细胞活化和炎症的面积。总的来说,这些结果表明血管支架在修复脊髓损伤中的潜力。我们的结果表明,在体外和在亚急性挫伤性脊髓损伤的大鼠模型中,可在肽支架内形成具有紧密连接并引起血脊髓屏障的血管系统。组织学分析表明,微血管的存在促进轴突渗透到损伤部位,并减少星形胶质细胞活化和炎症的面积。总的来说,这些结果表明血管支架在修复脊髓损伤中的潜力。
更新日期:2020-01-04
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