中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3620-3628.doi: 10.4103/NRR.NRR-D-24-00497

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

创伤性脑损伤后的神经再生：构建生物工程三维类人脑组织模型的方法

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Methods for a bioengineered 3D human brain-like tissue model of neuroregeneration after traumatic brain injury

Marly Coe1, Sydni Rosenfeld1, Celia Byrne1, Volha Liaudanskaya2, David L. Kaplan1, *   

  1. 1Department of Biomedical Engineering, Tufts University, Medford, MA, USA;  2Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA
  • Online:2026-08-18 Published:2026-04-27
  • Contact: David L. Kaplan, PhD, david.kaplan@tufts.edu.
  • Supported by:
    This work was supported by funding from the U.S. Department of Defense, Nos. W911NF-23-1-0276, W81XWH2211065 and the NIH, No. P41EB027062 (all to DLK).

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摘要：

创伤性脑损伤（TBI）会造成永久性细胞死亡，并可能导致长期认知功能障碍，而目前尚无修复受损脑组织的治疗方法。由于无法获得活体脑组织，跟踪和了解人类创伤性脑损伤的方法受到严重限制，因此需要体外模型系统来研究损伤后变性和再生的细胞机制。实验介绍了建立三维人脑组织模型的方法，该模型由丝-胶原复合支架组成，上面接种有人类神经元、星形胶质细胞和小胶质细胞，用于研究创伤后的神经再生。实验逐步描述了三维 “triculture ”系统的制造、损伤和分析评估过程。利用这种组织模型系统，证明了神经胶质细胞在受伤后的几周内促进了受伤部位神经元网络的再生。实验还发现三维组织中的再生网络不会分泌神经退行性疾病的早期标志物，但会显示兴奋/抑制失衡的迹象，这表明未来治疗创伤性脑损伤的促进再生疗法可能需要引导细胞分化以促进正常功能。该模型系统的机械稳定性使其具有与生理相关的冲击损伤和长期培养能力，而其模块化设计则使细胞内容物、细胞外基质成分和支架特性的改变成为可能。这种适应性可以整合患者来源的细胞和基因修饰，从而在以个性化靶向治疗为重点的研究和临床应用之间架起桥梁。该体外系统为加速创伤性脑损伤和神经退行性疾病的治疗进展提供了一个宝贵的平台，最终可改善患者的预后。


https://orcid.org/0000-0002-9245-7774 (David L. Kaplan)

关键词: 三维模型, 兴奋毒性, 神经胶质细胞, 人脑, 体外模型, 神经变性, 神经元网络, 再生, 组织工程, 创伤性脑损伤

Abstract: Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction, with no available treatments to repair the damaged brain tissue. Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue, creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury. Here we describe methods to establish a 3D human brain tissue model, consisting of a silk-collagen composite scaffold seeded with human neurons, astrocytes, and microglia, to study neuro-regeneration after traumatic brain injury. Step-by-step fabrication, injury, and analytical assessments of the 3D “triculture” system are described. Using this tissue model system, we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury. Further, we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease, but displayed signs of excitatory/inhibitory imbalance, suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function. The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability, while its modular design enables modification of cell contents, extracellular matrix composition, and scaffold properties. This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies. This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders, ultimately improving patient outcomes.

Key words: 3D model, excitotoxicity, glial cells, human brain, in vitro model, neurodegeneration, neuronal networks, regeneration, tissue engineering, traumatic brain injury