Circulating monocytes infiltrate and coordinate immune responses in tissues surrounding implanted biomaterials and in other inflamed tissues. Here we show that immunometabolic cues in the biomaterial microenvironment govern the trafficking of immune cells, including neutrophils and monocytes, in a manner dependent on the chemokine receptor 2 (CCR2) and the C-X3-C motif chemokine receptor 1 (CX3CR1). This affects the composition and activation states of macrophage and dendritic cell populations, ultimately orchestrating the relative composition of pro-inflammatory, transitory and anti-inflammatory CCR2⁺, CX3CR1⁺ and CCR2⁺ CX3CR1⁺ immune cell populations. In amorphous polylactide implants, modifying immunometabolism by glycolytic inhibition drives a pro-regenerative microenvironment principally by myeloid cells. In crystalline polylactide implants, together with arginase-1-expressing myeloid cells, T helper 2 cells and γδ⁺ T cells producing interleukin-4 substantially contribute to shaping the metabolically reprogrammed pro-regenerative microenvironment. Our findings inform the premise that local metabolic states regulate inflammatory processes in the biomaterial microenvironment.

循环单核细胞浸润并协调植入生物材料周围组织和其他发炎组织中的免疫反应。在这里，我们表明生物材料微环境中的免疫代谢线索以依赖于趋化因子受体 2 （CCR2） 和 C-X3-C 基序趋化因子受体 1 （CX3CR1） 的方式控制免疫细胞（包括中性粒细胞和单核细胞）的运输。这会影响巨噬细胞和树突状细胞群的组成和激活状态，最终协调促炎、暂时性和抗炎性 CCR2⁺、CX3CR1⁺ 和 CCR2⁺ CX3CR1⁺ 免疫细胞群的相对组成。在无定形聚丙交酯植入物中，通过糖酵解抑制修饰免疫代谢主要由髓系细胞驱动促再生微环境。在结晶聚丙交酯植入物中，与表达精氨酸酶 1 的髓系细胞一起，辅助性 T 细胞 2 细胞和产生白细胞介素-4 的 γδ⁺ T 细胞对塑造代谢重编程的促再生微环境有很大贡献。我们的研究结果为局部代谢状态调节生物材料微环境中的炎症过程提供了前提。