Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal
Anisotropic Alginate Hydrogels Promote Axonal Growth across Chronic Spinal Cord Transections after Scar Removal
复制标题
各向异性藻酸盐水凝胶促进疤痕去除后慢性脊髓横断的轴突生长
DOI：
10.1021/acsbiomaterials.9b01802
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发表时间：
2020-04-01
影响因子：
5.8
通讯作者：
Liu, Shengwen
中科院分区：
文献类型：
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作者：
Huang, Lulu;Wang, Yu;Liu, Shengwen
我们以前曾报道，含有各向异性毛细血管的藻酸盐水凝胶(AHS)可以恢复急性部分脊髓横断大鼠模型脊髓的连续性，并支持轴突再生。在没有额外促生长刺激的情况下，是否可以在完全慢性脊髓横断部位移植后发现类似的效果还没有被调查。因此，我们将AHS植入伤后4周瘢痕切除(SR)后的慢性胸部横断的腔内，并在植入后3个月内检测电生理和功能恢复以及AH支架内外下行和上升投射的再生。我们的结果表明，植入AH后，电生理导电性和运动功能均有明显改善。SR在手术后即刻会暂时损害运动功能，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移植物减少了损伤周围的纤维胶质细胞瘢痕。与皮质脊髓轴突相反，中缝脊髓和固有脊髓下行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。这些结果进一步支持了AHS的促再生特性及其与其他改善脊髓损伤后功能结果的策略相结合对慢性SCI的治疗潜力。
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.