Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization
Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization
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DOI：
10.1631/jzus.b2200447
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发表时间：
2023-06
影响因子：
5.1
通讯作者：
C. You;Zhi-Qing Zhu;Shuangshuang Wang;Xingang Wang;Chunmao Han;H. Shao
中科院分区：
文献类型：
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作者：
C. You;Zhi-Qing Zhu;Shuangshuang Wang;Xingang Wang;Chunmao Han;H. Shao
在组织工程支架的应用中，巨噬细胞引起的异物反应常导致伤口愈合延迟或失败。本研究探讨了纳米银（NAg）在减少支架移植过程中异物反应中的应用。采用冷冻干燥法制备NAg胶原-壳聚糖复合支架。将NAg-CCS植入大鼠背部，以评价对异物反应的影响。在不同的时间间隔收集皮肤组织样品用于组织学和免疫学评价。使用小型猪来评估NAg对皮肤伤口愈合的影响。在移植后的不同时间点对伤口拍照，并收集组织样品用于分子生物学分析。NAg-CCS具有多孔结构，可持续释放NAg两周。NAg-CCS组很少发生异物反应，而空白-CCS组在皮下移植实验中出现肉芽肿或坏死。NAg-CCS组基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）均显著降低。与空白CCS组相比，NAg-CCS组IL-10升高，IL-6降低。在伤口愈合研究中，NAg抑制M1巨噬细胞活化和炎症相关蛋白（诱导型一氧化氮合酶（iNOS）、IL-6和干扰素-γ（IFN-γ））。相比之下，M2巨噬细胞活化和促炎蛋白（促炎酶-1，主要组织相容性复合物-II（MHC-II），并在炎症区-1（FIZZ-1）中发现）得到促进，这是抑制异物反应和加速伤口愈合的原因。结论：含有NAg的真皮支架通过调节巨噬细胞和炎性细胞因子的表达抑制异物反应，从而促进伤口愈合。
Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds. This study explores the application of nanosilver (NAg) to reduce foreign body reactions during scaffold transplantation. An NAg hybrid collagen-chitosan scaffold (NAg-CCS) was prepared using the freeze-drying method. The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions. Skin tissue samples were collected for histological and immunological evaluation at variable intervals. Miniature pigs were used to assess the effects of NAg on skin wound healing. The wounds were photographed, and tissue samples were collected for molecular biological analysis at different time points post-transplantation. NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks. The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment. Both matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced significantly in the NAg-CCS group. The NAg-CCS group had higher interleukin (IL)-10 and lower IL-6 than the blank CCS group. In the wound healing study, M1 macrophage activation and inflammatory-related proteins (inducible nitric oxide synthase (iNOS), IL-6, and interferon-γ (IFN-γ)) were inhibited by NAg. In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted, and this was responsible for suppressing the foreign body responses and accelerating wound healing. In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.