Naturally-occurring bacterial cellulose-hyperbranched cationic polysaccharide derivative/MMP-9 siRNA composite dressing for wound healing enhancement in diabetic rats
Naturally-occurring bacterial cellulose-hyperbranched cationic polysaccharide derivative/MMP-9 siRNA composite dressing for wound healing enhancement in diabetic rats
复制标题
天然细菌纤维素-超支化阳离子多糖衍生物/MMP-9 siRNA复合敷料促进糖尿病大鼠伤口愈合
DOI：
10.1016/j.actbio.2019.11.005
复制
发表时间：
2020
影响因子：
9.7
通讯作者：
Yan Li
中科院分区：
文献类型：
--
作者：
Li Na;Yang Liqun;Pan Chenglin;Saw Phei Er;Ren Meng;Lan Biyun;Wu Junfeng;Wang Xiaoyi;Zeng Tingting;Zhou Liyan;Zhang Li-Ming;Yang Chuan;Yan Li
基质金属蛋白酶9（MMP-9）的异常高表达是阻碍糖尿病创面愈合的重要因素之一。因此，抑制MMP-9在糖尿病伤口中的表达可能是促进伤口愈合的可行方法。在这项研究中，我们研究了使用伤口敷料自我治疗的可能性，该伤口敷料含有细菌纤维素-超支化阳离子多糖（BC-HCP）衍生物，该衍生物包封siRNA（BC-HCP/siMMP-9）并具有控释特性。在此，我们使用四种HCP（Gly-DMAPA，Gly-D4，Amyp-DMAPA，Amyp-D4）作为基因载体。我们的研究结果表明，所有HCP衍生物在体外对细胞的毒性很小，而HCP的阳离子性质可以用作MMP-9 siRNA（siMMP-9）的络合剂。在暴露于细菌纤维素（BC）后，BC缓慢释放HCP/siMMP-9。释放的siMMP-9有效地降低了人永生化上皮细胞系（HaCAT）和糖尿病大鼠伤口中MMP-9的基因表达和蛋白水平。抑制糖尿病大鼠创面中的MMP-9导致创面愈合显著增强，表明BC-HCP/siMMP-9复合敷料可作为一种安全有效的敷料用于促进糖尿病大鼠创面愈合。我们评估了使用细菌纤维素-超支化阳离子多糖衍生物（BC-HCP）作为自-具有siRNA包封和控释性质的治疗性伤口敷料。我们的结果表明，BC-HCP/siMMP-9复合敷料缓慢释放HCP/siMMP-9。释放的siMMP-9有效地降低了人永生化上皮细胞系和糖尿病大鼠伤口中MMP-9的基因表达和蛋白水平。BC-HCP/siMMP-9复合敷料通过BC独特的纳米结构和释放siMMP-9以特异性抑制MMP-9来促进糖尿病伤口愈合。因此，它可以作为一种安全有效的敷料，以促进糖尿病大鼠的伤口愈合。这是关于使用BC作为敷料复合物的研究的第一个证据，通过封装HCP/siRNA复合物来有效沉默RNAi基因，从而改善糖尿病大鼠的伤口愈合。
AbstractsThe anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cellsin vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats.Statement of significanceIn this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.