Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2024-09-29 DOI:10.1016/j.biomaterials.2024.122855

Manisha Mahanty , Bidisha Dutta , Wenquan Ou , Xiaoping Zhu , Jonathan S. Bromberg , Xiaoming He , Shaik O. Rahaman

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Abstract

Host recognition and immune-mediated foreign body response (FBR) to biomaterials can adversely affect the functionality of implanted materials. FBR presents a complex bioengineering and medical challenge due to the lack of current treatments, making the detailed exploration of its molecular mechanisms crucial for developing new and effective therapies. To identify key molecular targets underlying the generation of FBR, here we perform analysis of microRNAs (miR) and mRNAs responses to implanted biomaterials. We found that (a) miR-146a levels inversely affect macrophage accumulation, foreign body giant cell (FBGC) formation, and fibrosis in a murine implant model; (b) macrophage-derived miR-146a is a crucial regulator of the FBR and FBGC formation, as confirmed by global and cell-specific knockout of miR-146a; (c) miR-146a modulates genes related to inflammation, fibrosis, and mechanosensing; (d) miR-146a modulates tissue stiffness near the implant during FBR as assessed by atomic force microscopy; and (e) miR-146a is linked to F-actin production and cellular traction force induction as determined by traction force microscopy, which are vital for FBGC formation. These novel findings suggest that targeting macrophage miR-146a could be a selective strategy to inhibit FBR, potentially improving the biocompatibility of biomaterials.

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巨噬细胞微RNA-146a是生物材料植入物异物反应的核心调节因子。

宿主对生物材料的识别和免疫介导的异物反应（FBR）会对植入材料的功能产生不利影响。由于目前缺乏治疗方法，异物反应是一项复杂的生物工程和医学挑战，因此详细探索其分子机制对于开发新的有效疗法至关重要。为了确定FBR产生的关键分子靶点，我们在此分析了微RNA（miR）和mRNA对植入生物材料的反应。我们发现：(a) 在小鼠植入物模型中，miR-146a 的水平与巨噬细胞积聚、异物巨细胞（FBGC）形成和纤维化成反比；(b) 巨噬细胞衍生的 miR-146a 是 FBR 和 FBGC 形成的关键调节因子，这一点已通过全面和细胞特异性敲除 miR-146a 得到证实；(c) miR-146a 可调节与炎症、纤维化和机械感应相关的基因；(d) 通过原子力显微镜评估，miR-146a 可调节 FBR 期间植入物附近的组织硬度；以及 (e) 通过牵引力显微镜测定，miR-146a 与 F-肌动蛋白的产生和细胞牵引力的诱导有关，而这对 FBGC 的形成至关重要。这些新发现表明，以巨噬细胞 miR-146a 为靶点可能是抑制 FBR 的一种选择性策略，有可能改善生物材料的生物相容性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.