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使用基于聚乳酸-羟基乙酸共聚物(PLGA)的电纺生物相容性沙格列汀纤维膜增强糖尿病伤口愈合

Enhanced Diabetic Wound Healing Using Electrospun Biocompatible PLGA-Based Saxagliptin Fibrous Membranes.

作者信息

Lee Chen-Hung, Huang Shu-Chun, Hung Kuo-Chun, Cho Chia-Jung, Liu Shih-Jung

机构信息

Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan.

Department of Physical Medicine and Rehabilitation, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan.

出版信息

Nanomaterials (Basel). 2022 Oct 25;12(21):3740. doi: 10.3390/nano12213740.

Abstract

Delayed diabetic wound healing is an adverse event that frequently leads to limb disability or loss. A novel and promising vehicle for the treatment of diabetic wounds is required for clinical purposes. The biocompatible and resorbable poly (lactic-co-glycolic acid) (PLGA)-based fibrous membranes prepared by electrospinning that provide a sustained discharge of saxagliptin for diabetic wound healing were fabricated. The concentration of released saxagliptin in Dulbecco’s phosphate-buffered saline was analyzed for 30 days using high-performance liquid chromatography. The effectiveness of the eluted saxagliptin was identified using an endothelial progenitor cell migration assay in vitro and a diabetic wound healing in vivo. Greater hydrophilicity and water storage were shown in the saxagliptin-incorporated PLGA membranes than in the pristine PLGA membranes (both p < 0.001). For diabetic wound healing, the saxagliptin membranes accelerated the wound closure rate, the dermal thickness, and the heme oxygenase-1 level over the follicle areas compared to those in the pristine PLGA group at two weeks post-treatment. The saxagliptin group also had remarkably higher expressions of insulin-like growth factor I expression and transforming growth factor-β1 than the control group (p = 0.009 and p < 0.001, respectively) in diabetic wounds after treatment. The electrospun PLGA-based saxagliptin membranes exhibited excellent biomechanical and biological features that enhanced diabetic wound closure and increased the antioxidant activity, cellular granulation, and functionality.

摘要

糖尿病伤口愈合延迟是一种不良事件,常导致肢体残疾或丧失。临床上需要一种新型且有前景的治疗糖尿病伤口的载体。通过静电纺丝制备了基于生物相容性和可吸收的聚(乳酸-乙醇酸)(PLGA)的纤维膜,其可为糖尿病伤口愈合提供持续释放的沙格列汀。使用高效液相色谱法分析了在杜尔贝科磷酸盐缓冲盐水中30天内释放的沙格列汀浓度。通过体外内皮祖细胞迁移试验和体内糖尿病伤口愈合试验确定了洗脱的沙格列汀的有效性。与原始PLGA膜相比,含沙格列汀的PLGA膜表现出更大的亲水性和储水性(两者p<0.001)。在治疗后两周,与原始PLGA组相比,沙格列汀膜在糖尿病伤口愈合方面加快了伤口闭合率、真皮厚度以及毛囊区域的血红素加氧酶-1水平。治疗后,沙格列汀组在糖尿病伤口中的胰岛素样生长因子I表达和转化生长因子-β1表达也显著高于对照组(分别为p = 0.009和p<0.001)。基于静电纺丝PLGA的沙格列汀膜表现出优异的生物力学和生物学特性,可促进糖尿病伤口闭合并提高抗氧化活性、细胞肉芽形成和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9522/9659155/cd09b3f346bc/nanomaterials-12-03740-g001.jpg

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