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一种通过在固定有Ce6的水凝胶中利用光触发的活性氧来对抗细菌感染的有前景的策略。

A promising strategy for combating bacterial infections through the use of light-triggered ROS in Ce6-immobilized hydrogels.

作者信息

Hong Seung Hee, Lee Mi Hee, Go Eun Jeong, Park Jong-Chul

机构信息

Department of Medical Engineering, Yonsei University, College of Medicine, Seoul 03722, Republic of Korea.

Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University, College of Medicine, Seoul 03722, Republic of Korea.

出版信息

Regen Biomater. 2024 Aug 23;11:rbae101. doi: 10.1093/rb/rbae101. eCollection 2024.

Abstract

The reactive oxygen species (ROS) are composed of highly reactive molecules, including superoxide anions ( ), hydrogen peroxide (HO) and hydroxyl radicals. Researchers have explored the potential benefits of using hydrogel dressings that incorporate active substances to accelerate wound healing. The present investigation involved the development of a hyaluronic acid (HA) hydrogel capable of producing ROS using LED irradiation. The process of creating a composite hydrogel was created by chemically bonding Ce6 to an amide group. Our analysis revealed that the synthesized hydrogel had a well-structured amide bond, and the degree of cross-linking was assessed through swelling, enzyme stability and cytotoxicity tests. ROS production was found to be influenced by both the intensity and duration of light exposure. Furthermore, in situations where cell toxicity resulting from ROS generation in the hydrogel surpassed 70%, no detectable genotoxic consequences were evident, and antibacterial activity was confirmed to be directly caused by the destruction of bacterial membranes as a result of ROS damage. Furthermore, the utilization of the generated ROS influences the polarization of macrophages, resulting in the secretion of pro-inflammatory cytokines, which is a characteristic feature of M1 polarization. Subsequently, we validated the efficacy of a HA hydrogel that produces ROS to directly eradicate microorganisms. Furthermore, this hydrogel facilitated indirect antibacterial activity by stimulating macrophages to release pro-inflammatory cytokines. These cytokines are crucial for coordinating cell-mediated immune responses and for modulating the overall effectiveness of the immune system. Therefore, the Ce6-HA hydrogel has the potential to serve as an effective wound dressing solution for infected wounds because of its ability to produce substantial levels or a consistent supply.

摘要

活性氧(ROS)由高反应性分子组成,包括超氧阴离子( )、过氧化氢(HO)和羟基自由基。研究人员探索了使用含有活性物质的水凝胶敷料来加速伤口愈合的潜在益处。本研究涉及开发一种能够通过LED照射产生活性氧的透明质酸(HA)水凝胶。通过将Ce6化学键合到酰胺基团上创建复合水凝胶的过程。我们的分析表明,合成的水凝胶具有结构良好的酰胺键,并通过溶胀、酶稳定性和细胞毒性测试评估交联度。发现活性氧的产生受光照强度和持续时间的影响。此外,在水凝胶中产生活性氧导致的细胞毒性超过70%的情况下,没有明显的可检测到的遗传毒性后果,并且证实抗菌活性是由于活性氧损伤导致细菌膜破坏直接引起的。此外,所产生的活性氧的利用影响巨噬细胞的极化,导致促炎细胞因子的分泌,这是M1极化的一个特征。随后,我们验证了产生活性氧的HA水凝胶直接根除微生物的功效。此外,这种水凝胶通过刺激巨噬细胞释放促炎细胞因子促进间接抗菌活性。这些细胞因子对于协调细胞介导的免疫反应和调节免疫系统的整体有效性至关重要。因此,Ce6-HA水凝胶由于其能够产生大量或持续供应的活性氧,有潜力作为感染伤口的有效伤口敷料解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfcf/11424027/2222a515e0d0/rbae101f10.jpg

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