Gao Bicong, Ni Haifeng, Lai Junhong, Gao Ning, Luo Xinxin, Wang Ying, Chen Yani, Zhao Jiaying, Yu Zhou, Zhang Jing, Cai Wenjin, Yang Guoli
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.
Zhejiang Key Laboratory of Plastic Modification and Processing Technology, College of Materials Science & Engineering, Zhejiang University of Technology, Hangzhou, 310014, China.
Bioact Mater. 2025 Apr 22;50:382-395. doi: 10.1016/j.bioactmat.2025.04.022. eCollection 2025 Aug.
Following an injury at the implantation position, blood-material interactions form a fibrin architecture, which serves as the initial activator of foreign body response (FBR). However, there is limited knowledge regarding how the topography of fibrin architectures regulates macrophage behavior in mitigating FBR. Mechanical cues of the microenvironment have been reported to shape immune cell functions. Here, we investigated macrophage mechanobiology at the organelle level by constructing heterogeneous fibrin networks. Based on findings , we demonstrated that adhesion-mediated differentiation of mitochondrial function modulated macrophage polarization. The finite activation of integrin signaling upregulated transglutaminase 2 (Tgm2) in a trans-manner, augments PGC1α-mediated mitochondrial biogenesis. Our study highlighted the previously overlooked spatial structures of host proteins adsorbed on material surfaces, advocating for a paradigm shift in material design strategies, from focusing solely on physical properties to considering the modification of host proteins.
在植入部位受伤后，血液与材料的相互作用形成纤维蛋白结构，这是异物反应（FBR）的初始激活剂。然而，关于纤维蛋白结构的拓扑结构如何调节巨噬细胞行为以减轻FBR的知识有限。据报道，微环境的机械信号可塑造免疫细胞功能。在这里，我们通过构建异质纤维蛋白网络在细胞器水平上研究了巨噬细胞机械生物学。基于这些发现，我们证明了粘附介导的线粒体功能分化调节巨噬细胞极化。整合素信号的有限激活以反式方式上调转谷氨酰胺酶2（Tgm2），增强PGC1α介导的线粒体生物发生。我们的研究强调了材料表面吸附的宿主蛋白以前被忽视的空间结构，主张材料设计策略发生范式转变，从仅关注物理性质转向考虑宿主蛋白的修饰。
