Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice
Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice
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DOI：
10.1016/j.actbio.2013.04.019
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发表时间：
2013-08-01
影响因子：
9.7
通讯作者：
Soldani, Giorgio
中科院分区：
文献类型：
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作者：
Losi, Paola;Briganti, Enrica;Soldani, Giorgio
由于内源性生长因子的水平和活性降低，糖尿病性皮肤溃疡难以自发愈合。重组人血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）具有刺激细胞增殖和加速伤口愈合的作用。在不丧失生物活性的情况下，将VEGF和bFGF持续可控地直接递送至创面，可增强其生物效应。本研究的目的是开发一种含有聚（醚）聚氨酯-聚二甲基硅氧烷/纤维蛋白的支架，该支架含有负载VEGF和bFGF（支架/ gf负载的NPs）的聚（乳酸-羟基乙酸）（PLGA）纳米颗粒，并评估其在遗传性糖尿病小鼠中的伤口愈合性能（db/db）。与不含生长因子（对照支架）或含有未加载的PLGA纳米颗粒（支架/未加载的NPs）的支架相比，将支架应用于全层背侧皮肤伤口，在第15天显著加速了伤口的愈合。然而，闭合率与使用含有游离VEGF和bFGF （scaffold/GFs）的支架处理的小鼠相似。组织学分析显示，两种含有生长因子的支架均诱导了完全的再上皮化，与其他组相比，肉芽组织形成/成熟度和胶原沉积增强。在糖尿病小鼠模型中，支架/ gf负载NPs促进伤口愈合的能力表明其作为糖尿病足溃疡患者敷料的潜在用途。(C) 2013材料学报Elsevier Ltd.出版。版权所有。
Diabetic skin ulcers are difficult to heal spontaneously due to the reduced levels and activity of endogenous growth factors. Recombinant human vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are known to stimulate cell proliferation and accelerate wound healing. Direct delivery of VEGF and bFGF at the wound site in a sustained and controllable way without loss of bioactivity would enhance their biological effects. The aim of this study was to develop a poly(ether)urethane-polydimethylsiloxane/fibrin-based scaffold containing poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with VEGF and bFGF (scaffold/GF-loaded NPs) and to evaluate its wound healing properties in genetically diabetic mice (db/db). The scaffold application on full-thickness dorsal skin wounds significantly accelerated wound closure at day 15 compared to scaffolds without growth factors (control scaffold) or containing unloaded PLGA nanoparticles (scaffold/unloaded NPs). However, the closure rate was similar to that observed in mice treated with scaffolds containing free VEGF and bFGF (scaffold/GFs). Both scaffolds containing growth factors induced complete re-epithelialization, with enhanced granulation tissue formation/maturity and collagen deposition compared to the other groups, as revealed by histological analysis. The ability of the scaffold/GF-loaded NPs to promote wound healing in a diabetic mouse model suggests its potential use as a dressing in patients with diabetic foot ulcers. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.