Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

巨噬细胞在体内植入后，在宿主组织对生物材料的反应中起着至关重要的作用。然而，在原位植入的生物材料周围积聚的生物材料降解相关巨噬细胞亚群的复杂性尚不完全清楚。在这里，我们使用单细胞 RNA-seq 分析支架周围各种细胞类型的转录组谱，以无偏见的方法绘制支架诱导的反应图。这使得能够以高分辨率绘制所有生物材料降解相关细胞，揭示组织驻留巨噬细胞的不同亚群作为生物材料原位降解的主要细胞来源。我们还发现支架结构会影响机械转导和特定材料降解相关巨噬细胞亚群的分解代谢活性以 Itgav-Mapk1-Stat3 依赖性方式，最终导致体内支架降解率的差异。我们的工作在单细胞水平上剖析了生物材料降解的细胞和分子基础的意外方面，并为未来开发功能性组织工程支架提供了一个概念框架。