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): 3706-3716.doi: 10.4103/NRR.NRR-D-25-00067

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

 搭载干扰素调节因子4的3D打印支架调节巨噬细胞极化促进损伤脊髓修复

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Interferon regulatory factor 4–releasing 3D-printed scaffolds enhance spinal cord repair by modulating macrophage polarization

Jianhao Wang1, 2, #, Jiawei Du1, #, Tuo Fang1, Di Zhang1, Yigang Lv1, Zhongju Shi1, *, Hengxing Zhou3, *, Shiqing Feng1, 3, 4, 5, *   

  1. 1Department of Orthopedics, Tianjin Medical University General Hospital, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, China; 
    2Department of Spine Surgery, Peking University People’s Hospital, Beijing, China; 
    3Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; 
    4Department of Orthopedics, the Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; 
    5Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Zhongju Shi, PhD, fantasyszj@126.com; Hengxing Zhou, PhD, zhouhengxing@sdu.edu.cn; Shiqing Feng, PhD, sqfeng@tmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81930070 (to SF), 82002309 (to ZS); the Tianjin Key Medical Discipline (Specialty) Construct Project, No. TJYXZDXK-027A (to SF); and a grant from Tianjin Institute of Orthopedic Innovation and Transformation (to SF).

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摘要：

3D打印水凝胶支架在脊髓损伤修复中应用广泛，GelMA因其生物性能优异。但传统支架与组织接触面积小，缺乏对炎症微环境的调控，需构建具有药物递送和免疫调控功能的智能支架。因此，实验开发了一种搭载干扰素调节因子4蛋白的3D打印甲基丙烯酰化明胶支架，以实现干扰素调节因子4的靶向和持续释放。该支架展现出良好的力学性能、生物相容性及持续释放干扰素调节因子4的能力。缓释的干扰素调节因子4蛋白通过竞争性结合髓样分化因子88抑制干扰素调节因子5的促炎作用，并通过激活信号转导与转录激活因子6通路促进M2型巨噬细胞极化，从而促进神经再生和脊髓功能恢复。表明构建的搭载干扰素调节因子43D打印甲基丙烯酰化明胶支架可通过干扰素调节因子4/干扰素调节因子5轴调节巨噬细胞的极化，改善脊髓损伤后炎症微环境，从而为改善炎症微环境促进神经再生提供新的靶点


https://orcid.org/0000-0001-9169-5319 (Zhongju Shi); 

https://orcid.org/0000-0003-0053-8970 (Hengxing Zhou); 

https://orcid.org/0000-0001-9437-7674 (Shiqing Feng)

关键词: 3D打印支架, 抗炎极化, 凋亡, 星形胶质细胞, 炎症微环境, 巨噬细胞极化, 小胶质细胞, 神经再生, 脊髓损伤

Abstract: Three-dimensional (3D)-printed hydrogel scaffolds are widely used in spinal cord injury repair, with gelatin methacrylate being particularly favored owing to its excellent biocompatibility. However, traditional scaffolds have a small contact area with tissues and lack the ability to regulate the inflammatory microenvironment. Therefore, there is a need to develop smart scaffolds with drug delivery and immune regulation functions. In this study, a 3D-printed gelatin methacrylate scaffold was developed to deliver interferon regulatory factor 4 in a targeted and sustained manner. The scaffold showed good mechanical properties, biocompatibility, and sustained interferon regulatory factor 4 release. The sustained-release interferon regulatory factor 4 competitively bound to myeloid differentiation factor 88 to inhibit the pro-inflammatory effects of interferon regulatory factor 5, and activated the signal transducer and activator of transcription 6 pathway to promote M2 macrophage polarization, thereby facilitating neural regeneration and recovery of spinal cord function. This indicates that the constructed interferon regulatory factor 4-loaded 3D-printed methyl acrylate-modified gelatin scaffold can regulate macrophage polarization through the interferon regulatory factor 4/5 axis, improve the inflammatory microenvironment after spinal cord injury, and thus provide a new target for promoting neural regeneration.

Key words: 3D-printed scaffold, inflammatory microenvironment, interferon regulatory factor 4, JAK1/STAT6 signaling pathway, macrophage polarization, microglia, nerve regeneration, spinal cord injury