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载有 PLGA-PTX/SDF-1α 的 3D 胶原多孔支架募集并促进神经干细胞分化,用于脊髓损伤修复。

3D collagen porous scaffold carrying PLGA-PTX/SDF-1α recruits and promotes neural stem cell differentiation for spinal cord injury repair.

机构信息

School of Life Sciences, Bengbu Medical College, Bengbu, China.

Department of Orthopedics and Department of Plastic Surgery, The First Affiliated Hospital, Bengbu Medical College, Bengbu, China.

出版信息

J Biomater Sci Polym Ed. 2023 Dec;34(17):2332-2355. doi: 10.1080/09205063.2023.2247715. Epub 2023 Aug 21.

Abstract

Spinal Cord Injury (SCI), one of the major factors of disability, can cause irreversible motor and sensory impairment. There are no effective therapeutic drugs and technologies available in domestic or foreign countries currently. Neural stem cells (NSCs), with the potential for multidirectional differentiation, are a potential treatment for SCI. However, it has been demonstrated that NSCs primarily differentiated into astrocytes rather than neurons due to the inflammatory microenvironment, and the current challenge remains to direct the differentiation of NSCs into neurons in the lesion site. It was reported that the microtubule-stabilizing agent paclitaxel (PTX) was able to promote the differentiation of NSCs into neurons rather than astrocytes after SCI. SDF-1α can recruit NSCs and thus guide the migration of stem cells. In this study, we developed a functional collagen scaffold by loading SDF-1α and nanoparticle-encapsulated PLGA-PTX into a 3D collagen porous scaffold, allowing for slow release of PTX. When the functional scaffolds were implanted into the injury site, it provided a neural regeneration conduit channel for the migration of NSCs and neuronal differentiation. Neural regeneration promoted the recovery of motor function and reduced glial scar formation after SCI. In conclusion, a 3D collagen porous scaffold combined with PLGA-PTX and SDF-1α is a promising therapeutic strategy for SCI repair.

摘要

脊髓损伤(SCI)是导致残疾的主要因素之一,可导致不可逆转的运动和感觉功能障碍。目前国内外尚无有效的治疗药物和技术。神经干细胞(NSCs)具有多向分化潜能,是 SCI 的一种潜在治疗方法。然而,已经证明 NSCs 主要分化为星形胶质细胞而不是神经元,这是由于炎症微环境,目前的挑战仍然是在损伤部位将 NSCs 定向分化为神经元。有报道称,微管稳定剂紫杉醇(PTX)在 SCI 后能够促进 NSCs 分化为神经元而不是星形胶质细胞。SDF-1α 可以募集 NSCs,从而指导干细胞的迁移。在本研究中,我们通过将 SDF-1α 和载有纳米颗粒的 PLGA-PTX 加载到 3D 胶原多孔支架中,开发了一种功能化的胶原支架,允许 PTX 缓慢释放。当功能支架被植入损伤部位时,它为 NSCs 的迁移和神经元分化提供了一个神经再生导管通道。神经再生促进了 SCI 后运动功能的恢复和神经胶质瘢痕的形成。总之,PLGA-PTX 和 SDF-1α 联合的 3D 胶原多孔支架是修复 SCI 的一种很有前途的治疗策略。

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