An aligned porous electrospun fibrous membrane with controlled drug delivery - An efficient strategy to accelerate diabetic wound healing with improved angiogenesis
An aligned porous electrospun fibrous membrane with controlled drug delivery - An efficient strategy to accelerate diabetic wound healing with improved angiogenesis
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具有受控药物输送功能的对齐多孔电纺纤维膜 - 通过改善血管生成来加速糖尿病伤口愈合的有效策略
DOI：
10.1016/j.actbio.2018.02.010
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发表时间：
2018
影响因子：
9.7
通讯作者：
Ke Qinfei
中科院分区：
文献类型：
--
作者：
Ren Xiaozhi;Han Yiming;Wang Jie;Jiang Yuqi;Yi Zhengfang;Xu He;Ke Qinfei
糖尿病患者的慢性伤口通常以血管生成不良和伤口愈合延迟为特征。探索有效的策略来显著改善糖尿病创面血管生成从而加速创面愈合仍然是一个重大的挑战。在此，我们报道了一种定向多孔聚乳酸（PlLA）电纺丝纤维膜，其中含有二甲基氧基酰甘氨酸（DMOG）负载的介孔二氧化硅纳米颗粒（DS），用于糖尿病伤口愈合。PlLA静电纺纤维呈单方向排列，纤维表面形成椭圆形纳米孔树脂，DS在纤维中分布良好，DMOG和Si的释放可以控制在纤维纳米孔中。体外实验结果表明，与纯PlLA膜相比，排列多孔复合膜（DS-PL）能促进人脐静脉内皮细胞（HUVECs）的增殖、迁移和血管生成相关基因的表达。他们的体内研究进一步表明，制备的DS-PL膜显著改善了糖尿病创面的新血管形成、再上皮化和胶原形成，并抑制了炎症反应，最终促进了糖尿病创面的愈合。总之，这些结果表明，层次结构（排列纤维上的纳米孔）与可控释放的DMOG药物以及膜上的Si离子相结合，可以产生快速刺激糖尿病伤口床血管生成的协同效应，是一种潜在的新型治疗策略，可以实现高效的糖尿病伤口愈合。意义声明糖尿病患者的慢性伤口通常以血管生成不良和伤口愈合延迟为特征。本研究的主要创新点是设计了一种新型的皮肤组织工程支架，即含有二甲基氧基酰甘氨酸（DMOG）负载介孔二氧化硅纳米颗粒（DS）的定向多孔聚乳酸（PlLA）电纺丝膜，可以显著改善糖尿病伤口床的血管生成，从而加速糖尿病伤口愈合。结果表明，表面具有椭圆型纳米孔的静电纺纤维呈单一方向排列，纤维中分布有DS粒子，DMOG和Si离子可以从纤维的纳米孔中可控地释放。他们的体外研究表明，DS-PL膜的分层纳米结构（排列纤维上的纳米孔）和可控释放的化学活性剂（DMOG药物和Si离子）在诱导内皮细胞增殖、迁移和分化方面发挥协同作用。综上所述，支架明显诱导了创面血管生成、胶原沉积和再上皮形成，并抑制了创面炎症反应，最终促进了糖尿病创面在体内的愈合。本研究的意义在于，将分层排列的多孔纳米纤维结构与负载dmog的msn结合在电纺丝纤维中，可能为慢性伤口愈合提供一种高效的策略。
A chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure. The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge. Herein, we reported a kind of aligned porous poly (l-lactic acid) (PlLA) electrospun fibrous membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS) for diabetic wound healing. The PlLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-poresin situgenerated onto the surface of fibers, while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers. Thein vitroresults revealed that the aligned porous composite membranes (DS-PL) could stimulate the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) compared with the pure PlLA membranes. Thein vivostudy further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization, re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed, which eventually stimulated the healing of the diabetic wound. Collectively, these results suggest that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable released DMOG drugs as well as Si ions from the membranes, which could create a synergetic effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a potential novel therapeutic strategy for highly efficient diabetic wound healing.Statement of SignificanceA chronic wound in diabetic patients is usually characterized by the poor angiogenesis and the delayed wound closure. The main innovation of this study is to design a new kind of skin tissue engineered scaffold, aligned porous poly (l-lactic acid) (PlLA) electrospun membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS), which could significantly improve angiogenesis in the diabetic wound bed and thereby accelerate diabetic wound healing. The results revealed that the electrospun fibers with ellipse-shaped nano-pores on the surface were aligned in a single direction, while there were DS particles distributed in the fibers and the DMOG as well as Si ions could be controllably released from the nanopores on the fibers. Thein vitrostudies demonstrated that the hierarchical nanostructures (nanopores on the aligned fibers) and the controllable released chemical active agents (DMOG drugs and Si ions) from the DS-PL membranes could exert a synergistic effect on inducing the endothelial cell proliferation, migration and differentiation. Above all, the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization as well as inhibited inflammation reaction in the wound sites, which eventually stimulated the healing of diabetic woundsin vivo. The significance of the current study is that the combination of the hierarchical aligned porous nanofibrous structure with DMOG-loaded MSNs incorporated in electrospun fibers may suggest a high-efficiency strategy for chronic wound healing.