da Silva Oliveira Victória Regina, Varsani Ridham, Zehra Mahjuba, Dale Camila Squarzoni, Arany Praveen
Oral Biology, Surgery, & Biomedical Engineering Departments, University at Buffalo, Buffalo, New York, USA.
Anatomy Department, Institute of Biomedical Science of University of São Paulo, São Paulo, Brazil.
Wound Repair Regen. 2025 Jul-Aug;33(4):e70068. doi: 10.1111/wrr.70068.
Diabetic ulcers resulting from neural and vascular perturbations represent a large proportion of non-traumatic lower limb amputations. Conventional treatments have limited efficacy. The non-invasive use of low-dose light treatments, termed photobiomodulation (PBM), has shown therapeutic benefits in diabetic patients. This study aimed to explore the response of endothelial cells to PBM treatment under hyperglycemic conditions in vitro. The major goal was to gain mechanistic insights into the biological effects of low-dose light, with the aim of optimising clinical treatment strategies. Therefore, human umbilical vein endothelial cells were exposed to hyperglycemic conditions (150-300 mM glucose) and incubated at 37°C with 5% CO for 24 h. The cells were then treated with low-dose light (660 nm, CW, 10 mW/cm, 200 s and 0.84 Einstein). Cell responses were assessed through key signalling pathways, evaluating proliferation using the AlamarBlue assay, migration through the wound scratch assay and angiogenesis via the tubulogenesis assay, with assessments after 24 or 48 h. Data were analysed using one-way ANOVA followed by Tukey's post-test. Data showed that PBM treatments performed under controlled thermal conditions significantly improved endothelial cell proliferation, migration and tubulogenesis under hyperglycemic conditions. Crosstalk among platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β1) signalling modulated these critical responses involving matrix metalloproteinases (MMP-2 and 9) activity. These findings showed that PBM treatments exert positive endothelial cell responses under hyperglycemic conditions that could contribute to improved diabetic wound healing. These observations provide mechanistic insights into enabling PBM as a novel and adjacent therapy for diabetic wound management.
由神经和血管紊乱导致的糖尿病溃疡占非创伤性下肢截肢的很大比例。传统治疗方法疗效有限。低剂量光疗法（称为光生物调节，PBM）的非侵入性应用已在糖尿病患者中显示出治疗益处。本研究旨在探讨体外高血糖条件下内皮细胞对PBM治疗的反应。主要目标是深入了解低剂量光的生物学效应机制，以优化临床治疗策略。因此，将人脐静脉内皮细胞置于高血糖条件下（150 - 300 mM葡萄糖），并在37°C、5% CO₂环境中孵育24小时。然后用低剂量光（660 nm，连续波，10 mW/cm²，200秒，0.84爱因斯坦）处理细胞。通过关键信号通路评估细胞反应，使用AlamarBlue检测法评估增殖，通过伤口划痕检测法评估迁移，通过管腔形成检测法评估血管生成，在24或48小时后进行评估。数据采用单因素方差分析，随后进行Tukey事后检验。数据表明，在可控热条件下进行的PBM治疗显著改善了高血糖条件下内皮细胞的增殖、迁移和管腔形成。血小板衍生生长因子（PDGF）、血管内皮生长因子（VEGF）和转化生长因子β（TGF-β1）信号通路之间的相互作用调节了这些涉及基质金属蛋白酶（MMP - 2和9）活性的关键反应。这些发现表明，PBM治疗在高血糖条件下对内皮细胞产生积极反应，这可能有助于改善糖尿病伤口愈合。这些观察结果为将PBM作为糖尿病伤口管理的一种新型辅助疗法提供了机制性见解。
