Institut des Neurosciences de la Timone, Aix-Marseille Université and CNRS UMR7289, 13005 Marseille, France.
Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, 13005 Marseille, France.
Cells. 2023 Mar 8;12(6):839. doi: 10.3390/cells12060839.
Poor functional recovery after spinal cord injury (SCI) drives the development of novel strategies to manage this devastating condition. We recently showed promising immunomodulatory and pro-regenerative actions of bio-functionalized carbon microfibres (MFs) implanted in a rodent model of SCI. In order to maximize tissue repair while easing MF implantation, we produced a composite implant based on the embedding of several MFs within a fibrin hydrogel. We used intravital imaging of fluorescent reporter mice at the early stages and spinal sections of the same animals 3 months later to characterize the neuroinflammatory response to the implant and its impact on axonal regeneration. Whereas fibrin alone was inert in the first week, its enzymatic degradation drove the chronic activation of microglial cells and axonal degeneration within 3 months. However, the presence of MFs inside the fibrin hydrogel slowed down fibrin degradation and boosted the early recruitment of immune cells. Noteworthy, there was an enhanced contribution of monocyte-derived dendritic cells (moDCs), preceding a faster transition toward an anti-inflammatory environment with increased axonal regeneration over 3 months. The inclusion of MF here ensured the long-term biocompatibility of fibrin hydrogels, which would otherwise preclude successful spinal cord regeneration.
脊髓损伤 (SCI) 后功能恢复不良促使人们开发新策略来治疗这种毁灭性疾病。我们最近在 SCI 的啮齿动物模型中显示了生物功能化碳纤维 (MF) 植入的有希望的免疫调节和促进再生作用。为了在减轻 MF 植入的同时最大限度地促进组织修复，我们制作了一种基于将几根 MF 嵌入纤维蛋白水凝胶中的复合植入物。我们使用荧光报告基因小鼠的活体成像，在早期和相同动物的脊髓切片 3 个月后，对植入物的神经炎症反应及其对轴突再生的影响进行了特征描述。尽管单独的纤维蛋白在第一周内是惰性的，但它的酶降解在 3 个月内导致小胶质细胞的慢性激活和轴突退化。然而，纤维蛋白水凝胶内 MF 的存在减缓了纤维蛋白的降解，并在 3 个月内促进了免疫细胞的早期募集。值得注意的是，单核细胞衍生的树突状细胞 (moDC) 的贡献增加，随后在 3 个月内更快地过渡到抗炎环境，轴突再生增加。这里 MF 的包含确保了纤维蛋白水凝胶的长期生物相容性，否则会妨碍成功的脊髓再生。
