Remodel Heterogeneous Electrical Microenvironment at Nano-Scale Interface Optimizes Osteogenesis by Coupling of Immunomodulation and Angiogenesis

IF 13 2区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Small Pub Date : 2024-12-18 DOI:10.1002/smll.202406090
Qingming Tang, Youzhun Fan, Jiwei Sun, Wenjie Fan, Baoying Zhao, Zhaoyi Yin, Yaru Cao, Yunyun Han, Bin Su, Cheng Yang, Peng Yu, Chengyun Ning, Lili Chen
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Abstract

Immunomodulation is essential for implants to regulate tissue regeneration, while bioelectricity plays a fundamental role in regulating immune activities. Under natural preferences, the bone matrix electrical microenvironment is heterogeneous in the nanoscale, which provides fundamental electrical cues to regulate bone immunity and regenerative repair. However, remodeling bone nanoscale heterogeneous electrical microenvironment remains a challenge, and the underlying immune modulation mechanism remains to be explored. In this research, in situ discretely distributed nano-heterojunctions are constructed on titanium oxide nanofibers to mimic the heterogeneous electrical microenvironment exhibited by bone collagen fibers. The material is identified to directly regulate calcium ion channeling for anti-inflammatory polarization of macrophages. Surprisingly, the highly biomimetic heterogeneous electrical microenvironment can induce a pro-angiogenic phenotypic transformation of macrophages, leading to enhanced neo-vascularization at the early stage of osteogenesis. Mechanistic exploration identifies that PI3K signaling pathway-mediated FGF2 secretion may partially explain for strengthened coupling of immunomodulation and angiogenesis, which optimizes subsequent bone regeneration. These findings highlight the significance of biomimetic heterogeneous electrical cues on immune-modulation and provide a design principle for future electroactive implant materials.

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在纳米级界面重构异质电微环境,通过免疫调节和血管生成的耦合优化成骨
免疫调节对于植入物调节组织再生至关重要,而生物电在调节免疫活动方面发挥着根本性作用。在自然偏好下,骨基质电微环境在纳米尺度上是异质的,这为调节骨免疫和再生修复提供了基本的电线索。然而,重塑骨纳米级异质电微环境仍是一个挑战,其背后的免疫调节机制仍有待探索。本研究在氧化钛纳米纤维上构建了原位离散分布的纳米异质结,以模拟骨胶原纤维所表现出的异质电微环境。经鉴定,该材料可直接调节钙离子通道,实现巨噬细胞的抗炎极化。令人惊讶的是,高度仿生的异质电微环境能诱导巨噬细胞发生促血管生成表型转化,从而在成骨早期阶段增强新血管生成。机制探索发现,PI3K 信号通路介导的 FGF2 分泌可部分解释免疫调节与血管生成之间的强化耦合,从而优化后续骨再生。这些发现强调了生物仿生异质电线索对免疫调节的重要意义,并为未来的电活性植入材料提供了设计原则。
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来源期刊
Small
Small 工程技术-材料科学:综合
CiteScore
17.70
自引率
3.80%
发文量
1830
审稿时长
2.1 months
期刊介绍: Small serves as an exceptional platform for both experimental and theoretical studies in fundamental and applied interdisciplinary research at the nano- and microscale. The journal offers a compelling mix of peer-reviewed Research Articles, Reviews, Perspectives, and Comments. With a remarkable 2022 Journal Impact Factor of 13.3 (Journal Citation Reports from Clarivate Analytics, 2023), Small remains among the top multidisciplinary journals, covering a wide range of topics at the interface of materials science, chemistry, physics, engineering, medicine, and biology. Small's readership includes biochemists, biologists, biomedical scientists, chemists, engineers, information technologists, materials scientists, physicists, and theoreticians alike.
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