Department of Functional Materials in Medicine and Dentistry at the Institute of Functional Materials and Biofabrication (IFB), University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Pleicherwall 2, D-97070, Würzburg, Germany.
Biocenter and Rudolf Virchow Center, University of Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
Biomaterials. 2022 Jun;285:121521. doi: 10.1016/j.biomaterials.2022.121521. Epub 2022 Apr 23.
As central part of the innate immune response, immune cells fight against invaders through various mechanisms, such as the release of extracellular traps (ETs). While this mechanism is mainly known for neutrophils in biomaterial contact, the release of macrophage extracellular traps (METs) in response to biomaterials has not yet been reported. An important application area for biomaterials is bone, where healing of defects of a critical size requires the implantation of grafts, which are often composed of calcium phosphates (CaPs). In this study, the response of human monocyte-derived macrophages in vitro to two different CaPs (α-tricalcium phosphate (α-TCP) and calcium deficient hydroxyapatite (CDHA)) as well as different pore structures was investigated. Scaffolds with anisotropic porosity were prepared by directional freezing, while samples with isotropic pore structure served as reference. It was revealed that ETs are released by human monocyte-derived macrophages in direct or indirect contact with CaP scaffolds. This was caused by mineral nanoparticles formed during incubation of α-TCP samples in culture medium supplemented with human platelet lysate, with an anisotropic pore structure attenuating MET formation. METs were significantly less pronounced or absent in association with CDHA samples. It was furthermore demonstrated that MET formation was accompanied by an increase in pro-inflammatory cytokines. Thus, this study provided the first evidence that macrophages are capable of releasing ETs in response to biomaterials.
作为先天免疫反应的核心部分，免疫细胞通过多种机制与入侵者作斗争，例如释放细胞外陷阱（ETs）。虽然这种机制主要在生物材料接触的中性粒细胞中为人所知，但目前尚未有关于巨噬细胞释放细胞外陷阱（METs）以响应生物材料的报道。生物材料的一个重要应用领域是骨骼，在骨骼中，对于临界尺寸的缺陷的愈合需要植入移植物，而这些移植物通常由磷酸钙（CaPs）组成。在这项研究中，研究了体外人单核细胞来源的巨噬细胞对两种不同的 CaP（α-磷酸三钙（α-TCP）和钙缺乏羟基磷灰石（CDHA））以及不同的孔结构的反应。各向异性多孔支架通过定向冷冻制备，而具有各向同性孔结构的样品则作为对照。结果表明，人单核细胞来源的巨噬细胞在与 CaP 支架直接或间接接触时会释放 ETs。这是由于在含有人血小板裂解物的培养基中孵育α-TCP 样品时形成了矿物质纳米颗粒，各向异性孔结构减弱了 MET 的形成。与 CDHA 样品相关联时，MET 的形成明显较少或不存在。此外，研究还表明 MET 的形成伴随着促炎细胞因子的增加。因此，本研究首次证明巨噬细胞能够响应生物材料释放 ETs。
