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
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Program in Human Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.
Biomedicines. 2021 Apr 27;9(5):479. doi: 10.3390/biomedicines9050479.
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.
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。