Department of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden.
ACS Appl Bio Mater. 2021 Sep 20;4(9):6791-6798. doi: 10.1021/acsabm.1c00513. Epub 2021 Aug 20.
Macrophages play a key role in determining the fate of implanted biomaterials, especially for biomaterials such as calcium phosphates (CaPs) where these cells play a vital role in material resorption and osteogenesis, as shown in different models, including clinical samples. Although substantial consideration is given to the design and validation of different CaPs, relatively little is known about their material-cell interaction. Specifically, the intracellular content of different CaP phases remains to be assessed, even though CaP-filled macrophages have been observed in several studies. In this study, 2D/3D ToF-SIMS imaging and multivariate analysis were directly applied on the histology samples of an explant to reveal the content of macrophages. The cellular content of the macrophages was analyzed to distinguish three CaP phases, monetite, beta-tricalcium phosphate, and pyrophosphate, which are all part of the monetite-based CaP implant composition under study. ToF-SIMS combined with histology revealed that the content of the identified macrophages was most similar to that of the pyrophosphate phase. This study is the first to uncover distinct CaP phases in macrophages from a human multiphasic CaP explant by targeted direct cell content analysis. The uncovering of pyrophosphate as the main phase found inside the macrophages is of great importance to understand the impact of the selected material in the process of biomaterial-instructed osteogenesis.
巨噬细胞在决定植入生物材料的命运方面起着关键作用，特别是对于磷酸钙（CaP）等生物材料，这些细胞在材料吸收和成骨过程中起着至关重要的作用，这在不同的模型中都有体现，包括临床样本。尽管人们对不同 CaP 的设计和验证给予了大量关注，但对它们的材料-细胞相互作用却知之甚少。具体来说，尽管在几项研究中已经观察到富含 CaP 的巨噬细胞，但不同 CaP 相的细胞内含量仍有待评估。在这项研究中，2D/3D ToF-SIMS 成像和多元分析直接应用于植入物的组织学样本，以揭示巨噬细胞的含量。分析了巨噬细胞的细胞含量，以区分三种 CaP 相，即单水磷酸氢钙、β-磷酸三钙和焦磷酸钙，它们都是研究中基于单水磷酸氢钙的 CaP 植入物成分的一部分。ToF-SIMS 结合组织学揭示，鉴定出的巨噬细胞的含量与焦磷酸钙相最为相似。本研究首次通过靶向直接细胞含量分析，从人类多相 CaP 植入物的巨噬细胞中揭示了不同的 CaP 相。在巨噬细胞内发现焦磷酸钙是主要相，这对于理解所选材料在生物材料指导成骨过程中的影响具有重要意义。
