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Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-02-21 , DOI: 10.1021/acsbiomaterials.9b01802
Lulu Huang 1 , Yu Wang 2 , Mingxin Zhu 2 , Xueyan Wan 2 , Huaqiu Zhang 2 , Ting Lei 2 , Armin Blesch 3 , Shengwen Liu 2
Affiliation  

We have previously reported that cell-seeded alginate hydrogels (AHs) with anisotropic capillaries can restore the continuity of the spinal cord and support axonal regeneration in a rat model of acute partial spinal cord transection. Whether similar effects can be found after transplantation into sites of complete chronic spinal cord transections without additional growth-promoting stimuli has not been investigated. We therefore implanted AHs into the cavity of a chronic thoracic transection following scar resection (SR) 4 weeks postinjury and examined electrophysiological and functional recovery as well as regeneration of descending and ascending projections within and beyond the AH scaffold up to 3 months after engraftment. Our results indicate that both electrophysiological conductivity and locomotor function are significantly improved after AH engraftment. SR transiently impairs locomotor function immediately after surgery but does not affect long-term outcomes. Histological analysis shows numerous host cells migrating into the scaffold channels and a reduction of fibroglial scaring around the lesion by AH grafts. In contrast to corticospinal axons, raphaespinal and propriospinal descending axons and ascending sensory axons regenerate throughout the scaffolds and extend into the distal host parenchyma. These results further support the pro-regenerative properties of AHs and their therapeutic potential for chronic SCI in combination with other strategies to improve functional outcomes after spinal cord injury.

中文翻译:

各向异性藻酸盐水凝胶促进瘢痕去除后跨慢性脊髓横断的轴突生长。

我们以前曾报道过,在具有急性部分脊髓横断的大鼠模型中,带有各向异性毛细管的细胞接种藻酸盐水凝胶(AHs)可以恢复脊髓的连续性并支持轴突再生。尚未研究在移植到完整的慢性脊髓横断位点而没有其他促进生长的刺激后是否会产生类似的效果。因此,我们将AHs植入伤后4周的瘢痕切除(SR)后的慢性胸腔横断腔中,并检查了其在植入后3个月内在AH支架内外的电生理和功能恢复以及下降和上升投射的再生。我们的结果表明,AH植入后,电生理传导性和运动功能均得到显着改善。SR会在手术后立即损害运动功能,但不会影响长期结果。组织学分析显示,大量宿主细胞迁移到支架通道中,AH移植物减少了病变周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反,肾上腺和脊柱下降轴突和上升感觉轴突在整个支架中再生并延伸到远端宿主实质中。这些结果进一步支持了AH的促再生特性及其对慢性SCI的治疗潜力,并结合其他改善脊髓损伤后功能结局的策略。SR会在手术后立即损害运动功能,但不会影响长期结果。组织学分析显示,大量宿主细胞迁移到支架通道中,AH移植物减少了病变周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反,肾上腺和脊柱下降轴突和上升感觉轴突在整个支架中再生并延伸到远端宿主实质中。这些结果进一步支持了AH的促再生特性及其对慢性SCI的治疗潜力,并结合其他改善脊髓损伤后功能结局的策略。SR会在手术后立即损害运动功能,但不会影响长期结果。组织学分析显示,大量宿主细胞迁移到支架通道中,AH移植物减少了病变周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反,肾上腺和脊柱下降轴突和上升感觉轴突在整个支架中再生并延伸到远端宿主实质中。这些结果进一步支持了AH的促再生特性及其对慢性SCI的治疗潜力,并结合其他改善脊髓损伤后功能结局的策略。组织学分析显示,大量宿主细胞迁移到支架通道中,AH移植物减少了病变周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反,肾上腺和脊柱下降轴突和上升感觉轴突在整个支架中再生并延伸到远端宿主实质中。这些结果进一步支持了AH的促再生特性及其对慢性SCI的治疗潜力,并结合其他改善脊髓损伤后功能结局的策略。组织学分析显示,大量宿主细胞迁移到支架通道中,AH移植物减少了病变周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反,肾上腺和脊柱下降轴突和上升感觉轴突在整个支架中再生并延伸到远端宿主实质中。这些结果进一步支持了AH的促再生特性及其对慢性SCI的治疗潜力,并结合其他改善脊髓损伤后功能结局的策略。
更新日期:2020-02-21
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