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用于骨再生的3D打印导电水凝胶支架:机电耦合、神经血管整合及免疫调节策略

3D-printed conductive hydrogel scaffolds for bone regeneration: Electromechanical coupling, neurovascular integration, and immunomodulatory strategies.

作者信息

Liu Yumiao, Li Longhui, Zhan Xiaoyu, Hong Susu, Chang Shaopeng, Huang Gan, Pan Shu-Ting, Liu Y, Li L, Zhan X, Hong S, Chang S, Huang G, Pan S

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China; Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330000, Jiangxi, China; Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

出版信息

Biomater Adv. 2026 Feb;179:214497. doi: 10.1016/j.bioadv.2025.214497. Epub 2025 Sep 9.

DOI:10.1016/j.bioadv.2025.214497
PMID:40957302
Abstract

Bone defect repair remains a formidable clinical challenge due to the limitations of traditional grafts and scaffolds, such as insufficient mechanical compatibility, minimal bioactivity, and poor biomimicry of bone's complex architecture. Emerging 3D-printed conductive hydrogel scaffolds offer a promising solution by combining the electroactive functionality of conductive materials with the cell-friendly, extracellular matrix-like properties of hydrogels. When fabricated into specific architectures via advanced 3D printing techniques, these composite scaffolds provide active biochemical and biophysical cues that enhance tissue regeneration. They can promote osteogenesis by activating key signaling pathways such as integrin-FAK-ERK and Piezo1/2-mediated calcium influx that upregulates osteogenic transcription factors. Simultaneously, they support neurogenesis and angiogenesis: the scaffold's conductivity and micro-topography guide neural differentiation and axon growth for nerve repair, while electrical stimulation and embedded conductive networks trigger the release of angiogenic factors to foster vascular network formation. These scaffolds also modulate the immune response, for example by polarizing macrophages toward a pro-regenerative M2 phenotype, thereby creating a more favorable healing microenvironment. As a result, 3D-printed conductive hydrogels can orchestrate bone regeneration in concert with vascularization and innervation, transcending the single-functionality of conventional scaffolds. Remaining challenges include ensuring long-term biocompatibility, achieving high-resolution microfabrication without compromising bioactivity, and optimizing electrical stimulation parameters for maximal regenerative benefit. Ongoing research is focused on developing bio-safe conductive composites, refining 3D printing methods, and employing dynamic stimulation strategies to address these challenges and accelerate the translation of conductive hydrogel scaffolds into clinical use.

摘要

由于传统移植物和支架存在局限性,如机械兼容性不足、生物活性最小化以及对骨复杂结构的仿生效果差,骨缺损修复仍然是一项艰巨的临床挑战。新兴的3D打印导电水凝胶支架通过将导电材料的电活性功能与水凝胶的细胞友好型、细胞外基质样特性相结合,提供了一种有前景的解决方案。当通过先进的3D打印技术制造成特定结构时,这些复合支架提供了活跃的生化和生物物理信号,可增强组织再生。它们可以通过激活关键信号通路来促进成骨,如整合素-FAK-ERK和Piezo1/2介导的钙内流,从而上调成骨转录因子。同时,它们支持神经发生和血管生成:支架的导电性和微观形貌引导神经分化和轴突生长以进行神经修复,而电刺激和嵌入的导电网络触发血管生成因子的释放以促进血管网络形成。这些支架还可以调节免疫反应,例如通过将巨噬细胞极化为促再生的M2表型,从而创造一个更有利于愈合的微环境。因此,3D打印导电水凝胶可以与血管化和神经支配协同协调骨再生,超越了传统支架的单一功能。仍然存在的挑战包括确保长期生物相容性、在不影响生物活性的情况下实现高分辨率微制造,以及优化电刺激参数以获得最大的再生效益。正在进行的研究集中在开发生物安全的导电复合材料、改进3D打印方法以及采用动态刺激策略来应对这些挑战,并加速导电水凝胶支架转化为临床应用。

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