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受结构启发的脊髓损伤内源性神经发生的谱系特异性基质

Structure-Inspired Lineage-Specific Matrix for Endogenous Neurogenesis in Spinal Cord Injury.

作者信息

Wu Bo, Lei Xuejiao, Ru Xufang, Zhou Jiangling, Liu Hao, Gan Yibo, Wang Yan, Li Wenyan

机构信息

School of Medicine, Nankai University, Tianjin 300071, China.

Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.

出版信息

Research (Wash D C). 2025 Aug 7;8:0821. doi: 10.34133/research.0821. eCollection 2025.

DOI:10.34133/research.0821
PMID:40777597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12329214/
Abstract

Spinal cord injury (SCI) poses substantial challenges, often leading to permanent disability and requiring adequate neuronal regeneration for functional repair. Decellularized spinal cord (DSC) matrices hold promise due to their native 3-dimensional (3D) structure and extracellular matrix (ECM)-derived biochemical components. However, their limited mechanical properties and insufficient availability of growth factors hinder their effectiveness. To address these limitations, this study introduces a core-shell design that reinforces DSC with a hydrogel-based matrix capable of delivering essential growth factors while preserving its natural structure. By leveraging 3D printing and electrostatic adsorption, the engineered matrix retains the topological features of DSC while introducing new topographical and neurogenic cues. These instructive cues facilitated an 11-fold increase in the number of newly generated neuronal cells, demonstrating lineage-specific neuronal regeneration in vivo. Mechanistically, the synergistic effects of ECM-inspired structure and biochemical cues activated the ITGA2/ITGA11-ERK/AKT signaling axis and promoted M2 macrophage/microglia polarization, thereby reducing cavity and scar formation. This optimized microenvironment enhanced endogenous neurogenesis and supported functional recovery after SCI. Overall, this study developed a structure-inspired lineage-specific matrix that effectively stimulates endogenous neuronal regeneration, highlighting its potential for advancing spinal cord repair strategies.

摘要

脊髓损伤（SCI）带来了巨大挑战，常常导致永久性残疾，并且需要足够的神经元再生以实现功能修复。去细胞脊髓（DSC）基质因其天然的三维（3D）结构和源自细胞外基质（ECM）的生化成分而具有应用前景。然而，它们有限的机械性能和生长因子的可用性不足阻碍了其有效性。为了解决这些局限性，本研究引入了一种核壳设计，用一种能够递送必需生长因子同时保留其天然结构的水凝胶基基质来增强DSC。通过利用3D打印和静电吸附，工程化基质保留了DSC的拓扑特征，同时引入了新的地形学和神经源性线索。这些指导性线索使新生成的神经元细胞数量增加了11倍，证明了体内谱系特异性神经元再生。从机制上讲，受ECM启发的结构和生化线索的协同作用激活了ITGA2/ITGA11-ERK/AKT信号轴，并促进了M2巨噬细胞/小胶质细胞极化，从而减少了空洞和瘢痕形成。这种优化的微环境增强了内源性神经发生，并支持了SCI后的功能恢复。总体而言，本研究开发了一种受结构启发的谱系特异性基质，可有效刺激内源性神经元再生，突出了其推进脊髓修复策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1ab/12329214/9d9117a8a64c/research.0821.fig.008.jpg
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