脊髓损伤(SCI)通常与瘢痕形成和空洞形成有关,因此桥接策略对于为轴突再生提供物理基础至关重要。在这项研究中,我们研究了由三亚甲基碳酸酯和ε-己内酯(TC)制成的可生物降解导管对成年大鼠SCI后再生的影响。体外研究表明,包括星形胶质细胞在内的不同细胞类型,脑膜成纤维细胞,施旺细胞和成体感觉背根神经节神经元可以在TC和PDO物资上生长。对于体内实验,TC/PDO导管在损伤后立即(急性SCI)或初次手术后2-5个月(慢性SCI)植入C3-C4宫颈段一个2-3mm长的小腔内.在植入急性SCI后8周,许多5HT阳性的下降的radaespinal轴突和感觉CGRP阳性的轴突通过导管再生,并且通常与PDO微丝和迁移的宿主细胞相关。植入慢性损伤的SCI诱导的再生主要是感觉CGRP阳性轴突。尽管与SCI对照相比,导管对OX42阳性小胶质细胞的密度没有影响,GFAP阳性星形胶质细胞的活性降低.结果表明,即使不添加外源性神经胶质细胞或干细胞,TC/PDO导管也可以支持急性和慢性SCI后的轴突再生。
生物合成导管可以支持脊髓损伤后的再生,但通常需要添加细胞疗法和神经营养因子。这项研究表明,由三亚甲基碳酸酯和ε-己内酯与聚对二恶烷酮微丝单独制成的可生物降解导管可以促进不同宿主细胞的迁移,并在植入急性和慢性脊髓损伤后刺激轴突再生。这些结果可用于开发用于未来临床应用的生物合成导管。
Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells.
Biosynthetic conduits can support regeneration after spinal cord injury but often require addition of cell therapy and neurotrophic factors. This study demonstrates that biodegradable conduits made from trimethylene carbonate and ε-caprolactone with poly-p-dioxanone microfilaments alone can promote migration of different host cells and stimulate axonal regeneration after implantation into acute and chronic spinal cord injury. These results can be used to develop biosynthetic conduits for future clinical applications.