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Functional reservoir microcapsules generated via microfluidic fabrication for long-term cardiovascular therapeutics.
Lab on a Chip ( IF 6.1 ) Pub Date : 2020-06-26 , DOI: 10.1039/d0lc00296h
Ngoc-Duy Dinh 1 , Marek Kukumberg , Anh-Tuan Nguyen , Hamed Keramati , Song Guo , Dinh-Tuan Phan , Nurdiyana B Ja'Afar , Erik Birgersson , Hwa Liang Leo , Ruby Yun-Ju Huang , Theodoros Kofidis , Abdul Jalil Rufaihah , Chia-Hung Chen
Affiliation  

Cardiovascular disease is a chronic disease that leads to impaired cardiac function and requires long-term management to control its progression. Despite the importance of hydrogels for therapeutic applications, a contradiction between the size of a hydrogel and the amount of loaded drug has been encountered when using conventional fabrication methods. In this study, biocompatible reservoir microcapsules (diameter ∼100 μm) with a large liquid core and polymeric shell were fabricated via a one-step phase separation of poly(ethylene glycol)diacrylate (PEGDA) and dextran within pre-gel droplets through microfluidics. By controlling the process of phase separation, high drug-loading efficiency (∼80%) for long-term release (30 days) of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was achieved. Drug molecules were dispersed within the liquid core at a concentration above saturation solubility for sustained delivery via regulation of the shells. Effective therapeutic enhancement of human umbilical vein endothelial cell (HUVEC) and umbilical artery smooth muscle cell (SMC) proliferation and tube formation in vitro promoted rapid cell proliferation and increased the number of migrated cells by ∼1.7 times. Moreover, in vivo blood vessel regeneration for cardiovascular control induced by sustained dual-drug (VEGF and PDGF) delivery to the rat heart was achieved, showing the effectiveness of long-term protein delivery in improving cardiac function and significantly reducing ventricular wall thickness and fibrosis of the infarct region. The ratio of heart tissue scarring was reduced to 11.2% after microcapsule treatment compared with 21.4% after saline treatment in the rat model. By using these reservoir microcapsules, similar sustained delivery of proteins, mRNAs and biologic drugs could be developed for the treatment of a range of long-term chronic diseases and regenerative medicine.

中文翻译:

通过微流体制造产生的功能性储库微胶囊,可用于长期心血管治疗。

心血管疾病是一种导致心脏功能受损的慢性疾病,需要长期管理才能控制其进展。尽管水凝胶对于治疗应用很重要,但是当使用常规的制备方法时,水凝胶的大小与载药量之间存在矛盾。在这项研究中,生物相容的微胶囊水库(直径约100微米)与一大的液体芯和聚合物外壳被制造通过通过微流控技术对预凝胶液滴中的聚乙二醇二丙烯酸酯(PEGDA)和右旋糖酐进行一步分离。通过控制相分离过程,可以实现长期释放(30天)血管内皮生长因子(VEGF)和血小板衍生生长因子(PDGF)的高载药率(〜80%)。药物分子以高于饱和溶解度的浓度分散在液核中,以通过调节壳来持续递送。人类的有效的治疗增强脐静脉内皮细胞(HUVEC)和脐动脉平滑肌细胞(SMC)增殖和管形成在体外促进快速细胞增殖和〜1.7倍增加的迁移细胞的数目。而且,体内实现了通过持续向大鼠心脏递送双重药物(VEGF和PDGF)诱导的心血管再生血管控制,显示了长期蛋白递送在改善心脏功能并显着降低心室壁厚度和梗死区域纤维化方面的有效性。大鼠模型中,微囊处理后心脏组织瘢痕形成的比例降低至11.2%,而盐水处理后为21.4%。通过使用这些储库微胶囊,可以开发出类似的蛋白质,mRNA和生物药物的持续递送方式,以治疗一系列长期慢性疾病和再生医学。
更新日期:2020-07-29
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