Yu Shuipeng, Zhang Qian, Hu Meilin, Zhao Borui, Liu Zhiyang, Li Changyi, Zhang Xi
School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China.
College of Electronic Information and Optical Engineering, Nankai University, Tianjin 300071, China.
Antibiotics (Basel). 2022 Oct 26;11(11):1482. doi: 10.3390/antibiotics11111482.
The bacterial invasions and inflammatory responses after implant placement often affect osseointegration; the increased secretion of pro-inflammatory cytokines can lead to poor formation of bone and bone absorption. Previous research has shown that the antimicrobial peptide 6K-F17 has antibacterial and immunomodulatory properties. The objective of this study was to optimize KR-1 and KR-2, based on 6K-F17, to apply to the tissue around the oral implant. Our first objective is to study its antibacterial properties, and then we intend to further study its osteogenic ability to osteoblasts by modulating the immune response of macrophages. In this research, KR-1 and KR-2 can inhibit the formation of bacterial biofilm, and further kill bacteria and by destroying the cell wall and cell membrane of bacteria. The novel peptides restrained the activation of the NF-κB signaling pathway by reducing the phosphorylation levels of IκBα and p65, inhibiting the degradation of IκBα and the nuclear translocation of p65, and increasing the percentage of M2 phenotype in macrophages. This suppressed the inflammatory response induced by lipopolysaccharides and enhanced the osteogenic activity of osteoblasts; this, in turn, promoted osteogenesis. The antimicrobial peptide KR-1 showed better performance. Our results demonstrate that KR-1 and KR-2 have antibacterial and bone immunomodulatory effects, and further promote osteogenesis by modulating the immune microenvironment, which provides the possibility for the adjuvant treatment of peri-implant diseases.
种植体植入后的细菌入侵和炎症反应常常会影响骨结合；促炎细胞因子分泌增加会导致骨形成不良和骨吸收。先前的研究表明，抗菌肽6K-F17具有抗菌和免疫调节特性。本研究的目的是在6K-F17的基础上优化KR-1和KR-2，以应用于口腔种植体周围组织。我们的首要目标是研究其抗菌特性，然后打算通过调节巨噬细胞的免疫反应进一步研究其对成骨细胞的成骨能力。在本研究中，KR-1和KR-2可抑制细菌生物膜的形成，并通过破坏细菌的细胞壁和细胞膜进一步杀灭细菌。这些新型肽通过降低IκBα和p65的磷酸化水平、抑制IκBα的降解和p65的核转位以及增加巨噬细胞中M2表型的百分比来抑制NF-κB信号通路的激活。这抑制了脂多糖诱导的炎症反应，增强了成骨细胞的成骨活性；进而促进了骨生成。抗菌肽KR-1表现出更好的性能。我们的结果表明，KR-1和KR-2具有抗菌和骨免疫调节作用，并通过调节免疫微环境进一步促进骨生成，这为种植体周围疾病的辅助治疗提供了可能性。
