Department of Preventive Dentistry, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China.
Department of The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.
Adv Healthc Mater. 2024 Jan;13(3):e2302256. doi: 10.1002/adhm.202302256. Epub 2023 Nov 20.
The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH-responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis-promotion material for diabetic wound healing. CMO exhibited pH-responsive release of Mo and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti-inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF-α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL-10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF-1α/VEGF pathway-a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.
糖尿病伤口的复杂创面环境导致治疗效果不佳，而炎症紊乱和血管损伤是此类患者死亡的主要原因。在此，专门开发了一种可喷涂的、可控制的自适应、pH 响应型钼酸盐和寡糖纳米系统（CMO），作为一种免疫调节和促进血管生成的材料，用于糖尿病伤口愈合。CMO 表现出 pH 响应性的 Mo 和寡糖（COS）释放，特别是对糖尿病伤口中观察到的碱性环境的响应。CMO 通过显著刺激巨噬细胞线粒体功能来促进 M2 极化，从而提供抗炎环境。具体而言，一定浓度的 CMO 可降低活性氧（ROS）和肿瘤坏死因子-α（TNF-α）的表达，并上调巨噬细胞中线粒体膜电位（MMP）、超氧化物歧化酶（SOD）和白细胞介素 10（IL-10）的表达。此外，CMO 通过上调 PI3K/HIF-1α/VEGF 通路促进血管生成，这是形成为愈合组织提供营养和氧气的新血管的关键过程。值得注意的是，CMO 促进内皮细胞的活力和迁移，并增强血管生成基因的表达。体外和体内研究表明，这种针对线粒体功能的简单但强大的纳米系统具有成为糖尿病伤口愈合有效治疗方法的潜力。
