INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Biomaterials. 2013 Dec;34(38):9952-9. doi: 10.1016/j.biomaterials.2013.09.012. Epub 2013 Sep 25.
Macrophages are a key cell in the host response to implants and can be polarized into different phenotypes capable of inducing both detrimental and beneficial outcomes in tissue repair and remodeling, being important in tissue engineering and regenerative medicine. The objective of this study was to evaluate the macrophage response to 3D porous chitosan (Ch) scaffolds with different degrees of acetylation (DA, 5% and 15%). The M1/M2 phenotypic polarization profile of macrophages was investigated in vivo using a rodent air-pouch model. Our results show that the DA affects the macrophage response. Ch scaffolds with DA 5% induced the adhesion of lower numbers of inflammatory cells, being the M2 the predominant phenotypic profile among the adherent macrophages. In the inflammatory exudates F4/80(+)/CD206(+) cells (M2 macrophages) appeared in higher numbers then F4/80(+)/CCR7(+) cells (M1 macrophages), in addition, lower levels of pro-inflammatory cytokines together with higher levels of anti-inflammatory cytokines were found. Ch scaffolds with DA 15% showed opposite results, since M1 were the predominant macrophages both adherent to the scaffold and in the exudates, together with high levels of pro-inflammatory cytokines. In conclusion, Ch scaffolds with DA 5% induced a benign M2 anti-inflammatory macrophage response, whereas Ch scaffolds with DA 15% caused a macrophage M1 pro-inflammatory response.
巨噬细胞是宿主对植入物反应的关键细胞，可极化为不同的表型，能够在组织修复和重塑中诱导有益和有害的结果，在组织工程和再生医学中具有重要作用。本研究的目的是评估不同乙酰化程度（DA，5%和 15%）的 3D 多孔壳聚糖（Ch）支架对巨噬细胞的反应。使用啮齿动物气囊模型在体内研究了巨噬细胞的 M1/M2 表型极化特征。结果表明，DA 会影响巨噬细胞的反应。DA 为 5%的 Ch 支架诱导较低数量的炎性细胞黏附，黏附的巨噬细胞中 M2 表型占主导地位。在炎症渗出物中，F4/80（+）/CD206（+）细胞（M2 巨噬细胞）的数量高于 F4/80（+）/CCR7（+）细胞（M1 巨噬细胞），此外，还发现促炎细胞因子水平降低，抗炎细胞因子水平升高。DA 为 15%的 Ch 支架则呈现相反的结果，因为黏附在支架上和渗出物中的主要巨噬细胞为 M1，同时伴有高水平的促炎细胞因子。总之，DA 为 5%的 Ch 支架诱导了良性的 M2 抗炎性巨噬细胞反应，而 DA 为 15%的 Ch 支架则引起了巨噬细胞 M1 促炎性反应。
