Dual-temporal bidirectional immunomodulation of Cu-Zn Bi-layer nanofibrous membranes for sequentially enhancing antibacterial activity and osteogenesis

Dual-temporal bidirectional immunomodulation of Cu-Zn Bi-layer nanofibrous membranes for sequentially enhancing antibacterial activity and osteogenesis
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双颞双向免疫调节铜锌双层纳米纤维膜依次增强抗菌活性和成骨作用

DOI:
10.1016/j.apmt.2020.100888
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发表时间:
2021-03-04
影响因子:
8.3
通讯作者:
Zhang, Xianlong
Zhang, Xianlong
中科院分区:
材料科学2区
文献类型:
--
作者:
Guo, Geyong;Xu, Qing;Zhang, Xianlong

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假体相关感染(IRIs)和假体骨整合障碍是全关节置换术(TJA)后最常见和最严重的并发症。巨噬细胞在这些并发症的发生中起着至关重要的作用。本文针对IRIs和种植体骨整合障碍的免疫学特点,采用静电纺丝和热压法制备Cu-Zn双层纳米纤维膜,提出了一种序次免疫调节策略来应对并发症。研究发现,Cu-Zn双层纳米纤维膜具有良好的Cu2+和Zn2+控释作用,并可通过交替激活MAPK和mTOR信号通路,调控巨噬细胞从M1向M2的表型转移。此外,Cu-Zn双层纳米纤维膜的双时间双向免疫调节作用使其具有良好的体外和体内抗感染和成骨能力。据我们所知,这是第一个专门为IRIs和种植体骨整合障碍的免疫需求设计的双时间双向免疫调节生物材料。这是一项有意义的尝试,为探索新型免疫调节生物材料解决临床难题铺平了新的道路。(C) 2020 Elsevier Ltd.版权所有。
Implant-related infections (IRIs) and implant osseointegration disorders are the most common and catastrophic complications after total joint arthroplasty (TJA). Macrophages play a vital role in the development of these complications. Herein, tailored to the immunological characteristics of IRIs and implant osseointegration disorders, we proposed a sequential immunomodulatory strategy to cope with the complications, using Cu-Zn bi-layer nanofibrous membranes synthesized via a facile electrospinning process and a hot-pressed method. It was found that Cu-Zn bi-layer nanofibrous membranes exhibited a desirable controlled release of Cu2+ and Zn2+, and could sequentially regulate macrophage phenotype shift from M1 to M2 through alternately activating the MAPK and mTOR signaling pathways. Moreover, the dual-temporal bidirectional immunomodulatory effect endowed the Cu-Zn bi-layer nanofibrous membranes excellent anti-infection and osteogenic abilities in vitro and in vivo. To our knowledge, this is the first dual-temporal bidirectional immunomodulatory biomaterial specifically designed for the immune requirements of IRIs and implant osseointegration disorders. This is a meaningful attempt, which may pave a new way for exploring novel immunomodulatory biomaterials to solve the clinical challenges. (C) 2020 Elsevier Ltd. All rights reserved.