Zhao Yuyu, Hang Ruiyue, Li Huifei, Sun Yonghua, Yao Runhua, Huang Xiaobo, Zhang Xiangyu, Yao Xiaohong, Wang Huaiyu, Xiao Yin, Huang Di, Han Yong, Wang Xing, Hang Ruiqiang
Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China.
School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, 030001, China.
Adv Sci (Weinh). 2025 Mar;12(10):e2409809. doi: 10.1002/advs.202409809. Epub 2025 Jan 21.
The interaction between biomaterials and immune system is a critical area of research, especially in tissue engineering and regenerative medicine. A fascinating and less explored aspect involves the immunomodulatory behaviors of macrophage (MΦ)-derived exosomes induced by biomaterial surfaces. Herein, untreated surface, nanostructured surface, and type I collagen (Col-I)-decorated nanostructured surface of titanium implants are chosen to culture MΦs, followed by extraction of MΦ-derived exosomes and investigation of their immunomodulatory functions and mechanisms. The results show that the exosomes in the untreated group carried plenty of inflammatory cytokines, predominantly C─C motif chemokine ligand 2 (CCL2). After targeting recipient cells, the CCL2 on the exosomes can specifically bind to its receptor C─C motif chemokine receptor 2, triggering downstream signaling pathways to induce internalization of membrane integrin β1 and targeted lysosomal degradation, consequently suppressing the functions of recipient cells. In contrast, the exosomes in the nanostructured group, especially Col-I-decorated nanostructured group carried few CCL2, moderating their inhibition on the functions of recipient cells. These findings not only clearly show that CCL2 is a key constituent of exosomes involved in the interaction between biomaterials and host immune system, but also potentially a key target for designing advanced biomaterials to promote tissue repair and regeneration.
生物材料与免疫系统之间的相互作用是一个关键的研究领域，尤其是在组织工程和再生医学方面。一个引人入胜但较少被探索的方面涉及生物材料表面诱导的巨噬细胞（MΦ）衍生外泌体的免疫调节行为。在此，选择钛植入物的未处理表面、纳米结构表面和I型胶原（Col-I）修饰的纳米结构表面来培养MΦ，随后提取MΦ衍生的外泌体并研究其免疫调节功能和机制。结果表明，未处理组的外泌体携带大量炎性细胞因子，主要是C-C基序趋化因子配体2（CCL2）。外泌体靶向受体细胞后，其上的CCL2可特异性结合其受体C-C基序趋化因子受体2，触发下游信号通路，诱导膜整合素β1内化和靶向溶酶体降解，从而抑制受体细胞的功能。相比之下，纳米结构组，尤其是Col-I修饰的纳米结构组的外泌体携带的CCL2较少，减轻了它们对受体细胞功能的抑制。这些发现不仅清楚地表明CCL2是参与生物材料与宿主免疫系统相互作用的外泌体的关键成分，而且可能是设计先进生物材料以促进组织修复和再生的关键靶点。
