Department of Biotechnology, National Institute of Pharmaceutical Educational and Research, Ahmedabad, Gandhinagar, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Educational and Research, Ahmedabad, Gandhinagar, India.
Biomater Adv. 2022 Aug;139:212971. doi: 10.1016/j.bioadv.2022.212971. Epub 2022 Jun 9.
Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function. The pathology of SCI is multifaceted and involves a cascade of events, including neuroinflammation and neuronal degeneration at the epicenter, limiting repair process. We developed a supermacroporous, mechanically elastic, electro-conductive, graphene crosslinked collagen (Gr-Col) cryogels for the regeneration of the spinal cord post-injury. The effects of graphene in controlling astrocytes reactivity and microglia polarization are evaluated in spinal cord slice organotypic culture and rat spinal cord lateral hemisection model of SCI. In our work, the application of external electric stimulus results in the enhanced expression of neuronal markers in an organotypic culture. The implantation of Gr-Col cryogels in rat thoracic T9-T11 hemisection model demonstrates an improved functional recovery within 14 days post-injury (DPI), promoted myelination, and decreases the lesion volume at the injury site. Decrease in the expression of STAT3 in the implanted Gr-Col cryogels may be responsible for the decrease in astrocytes reactivity. Microglia cells within the implanted cryogels shows higher anti-inflammatory phenotype (M2) than inflammatory (M1) phenotype. The higher expression of mature axonal markers like β-tubulin III, GAP43, doublecortin, and neurofilament 200 in the implanted Gr-Col cryogel confirms the axonal regeneration after 28 DPI. Gr-Col cryogels also modulate the production of ECM matrix, favouring the axonal regeneration. This study shows that Gr-Col cryogels decreases neuroinflammation and accelerate axonal regeneration.
脊髓损伤 (SCI) 是一种毁灭性的疾病，会导致运动功能丧失。SCI 的病理学是多方面的，涉及一系列事件，包括损伤中心的神经炎症和神经元变性，从而限制了修复过程。我们开发了一种超大孔、机械弹性、导电、石墨烯交联胶原 (Gr-Col) 冷冻凝胶，用于损伤后脊髓的再生。在脊髓切片器官培养和大鼠 SCI 脊髓侧半切模型中，评估了石墨烯在控制星形胶质细胞反应性和小胶质细胞极化中的作用。在我们的工作中，施加外部电刺激会导致器官培养物中神经元标志物的表达增强。Gr-Col 冷冻凝胶在大鼠胸 T9-T11 半切模型中的植入表明，在损伤后 14 天 (DPI) 内功能恢复得到改善，促进了髓鞘形成，并减少了损伤部位的病变体积。植入的 Gr-Col 冷冻凝胶中 STAT3 的表达减少可能是星形胶质细胞反应性降低的原因。植入的冷冻凝胶中的小胶质细胞表现出更高的抗炎表型 (M2)，而不是炎症表型 (M1)。植入的 Gr-Col 冷冻凝胶中β-微管蛋白 III、GAP43、双皮质素和神经丝 200 等成熟轴突标志物的高表达证实了 28 DPI 后的轴突再生。Gr-Col 冷冻凝胶还调节细胞外基质 (ECM) 基质的产生，有利于轴突再生。这项研究表明，Gr-Col 冷冻凝胶可减少神经炎症并加速轴突再生。
