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使用涂有细胞外基质蛋白的脊状支架促进神经元生长。

Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins.

作者信息

Siddiqui Ahad M, Brunner Rosa, Harris Gregory M, Miller Alan Lee, Waletzki Brian E, Schmeichel Ann M, Schwarzbauer Jean E, Schwartz Jeffrey, Yaszemski Michael J, Windebank Anthony J, Madigan Nicolas N

机构信息

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

Program in Human Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.

出版信息

Biomedicines. 2021 Apr 27;9(5):479. doi: 10.3390/biomedicines9050479.

Abstract

Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a limited ability to regenerate, and current clinical therapies for SCI are not effective in helping promote neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the biodegradable hydrogel oligo(poly(ethylene glycol)fumarate) (OPF). We have previously shown that positively charged OPF scaffolds (OPF+) in an open spaced, multichannel design can be loaded with Schwann cells to support axonal generation and functional recovery following SCI. We have now developed a hybrid OPF+ biomaterial that increases the surface area available for cell attachment and that contains an aligned microarchitecture and extracellular matrix (ECM) proteins to better support axonal regeneration. OPF+ was fabricated as 0.08 mm thick sheets containing 100 μm high polymer ridges that self-assemble into a spiral shape when hydrated. Laminin, fibronectin, or collagen I coating promoted neuron attachment and axonal outgrowth on the scaffold surface. In addition, the ridges aligned axons in a longitudinal bipolar orientation. Decreasing the space between the ridges increased the number of cells and neurites aligned in the direction of the ridge. Schwann cells seeded on laminin coated OPF+ sheets aligned along the ridges over a 6-day period and could myelinate dorsal root ganglion neurons over 4 weeks. This novel scaffold design, with closer spaced ridges and Schwann cells, is a novel biomaterial construct to promote regeneration after SCI.

摘要

脊髓损伤(SCI)会导致细胞死亡、脱髓鞘和轴突损失。脊髓的再生能力有限,目前针对SCI的临床治疗在促进神经功能恢复方面效果不佳。我们开发了一种新型的支架生物材料,它由可生物降解的水凝胶聚(乙二醇)富马酸酯(OPF)制成。我们之前已经表明,呈开放空间多通道设计的带正电荷的OPF支架(OPF+)可以负载雪旺细胞,以支持SCI后的轴突生成和功能恢复。我们现在开发了一种混合OPF+生物材料,它增加了可供细胞附着的表面积,并且包含排列整齐的微结构和细胞外基质(ECM)蛋白,以更好地支持轴突再生。OPF+被制作成0.08毫米厚的薄片,其中含有100微米高的聚合物脊,水化时会自组装成螺旋形状。层粘连蛋白、纤连蛋白或胶原蛋白I涂层促进了神经元在支架表面的附着和轴突生长。此外,这些脊使轴突呈纵向双极排列。减小脊之间的间距增加了沿脊方向排列的细胞和神经突的数量。接种在层粘连蛋白包被的OPF+薄片上的雪旺细胞在6天内沿脊排列,并且能够在4周内使背根神经节神经元髓鞘化。这种具有更近间距的脊和雪旺细胞的新型支架设计是一种促进SCI后再生的新型生物材料构建体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09b2/8146557/50bbc2ba7e5c/biomedicines-09-00479-g001.jpg

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