Injectable Citrate-Based Hydrogel as an Angiogenic Biomaterial Improves Cardiac Repair after Myocardial Infarction
Injectable Citrate-Based Hydrogel as an Angiogenic Biomaterial Improves Cardiac Repair after Myocardial Infarction
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可注射柠檬酸盐水凝胶作为血管生成生物材料可改善心肌梗塞后的心脏修复
DOI：
10.1021/acsami.9b12043
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xiaoyang Xu
中科院分区：
文献类型：
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作者：
Zhize Yuan;Yung-Hao Ysou;Xue-Qing Zhang;Shixing Huang;Yang Yang;Mingzhu Gao;William Ho;Qiang Zhao;Xiaofeng Ye;Xiaoyang Xu
植入的医用生物材料通过生物材料-细胞/组织的相互作用与宿主生物系统密切接触，这些相互作用在调节细胞功能和组织再生中起着关键作用。然而，许多生物材料随着时间的推移而降解，并且这些降解产物也被证明与宿主细胞/组织相互作用。因此，专门设计具有降解产物的植入生物材料可能是有用的，这将大大提高植入物的性能。在这里，我们报告了一种可注射的，含有柠檬酸盐的聚酯水凝胶，它可以通过水凝胶降解释放柠檬酸盐作为细胞调节剂，同时显示出包封生长因子Mydgf的持续释放。通过将水凝胶降解产物（柠檬酸盐）与包封Mydgf的治疗作用偶联，我们观察到大鼠心肌梗死（MI）模型中心肌梗死后心脏修复的改善。心肌内注射含有Mydgf的柠檬酸盐水凝胶可显著减少疤痕形成和梗死面积，增加壁厚和新生血管，并改善心脏功能。这种生物活性可注射的水凝胶介导的组合方法具有许多优点，包括可能调整给药速度和持续时间，改善治疗效果，以及微创给药。我们的合理设计结合了有益的降解产物和治疗药物的可控释放，为下一代生物材料提供了灵感，旨在彻底改变再生医学。
Implanted medical biomaterials are closely in contact with host biological systems via biomaterial−cell/tissue interactions, and these interactions play pivotal roles in regulating cell functions and tissue regeneration. However, many biomaterials degrade over time, and these degradation products also have been shown to interact with host cells/tissue. Therefore, it may prove useful to specifically design implanted biomaterials with degradation products which greatly improve the performance of the implant. Herein, we report an injectable, citrate-containing polyester hydrogel which can release citrate as a cell regulator via hydrogel degradation and simultaneously show sustained release of an encapsulated growth factor Mydgf. By coupling the therapeutic effect of the hydrogel degradation product (citrate) with encapsulated Mydgf, we observed improved postmyocardial infarction (MI) heart repair in a rat MI model. Intramyocardial injection of our Mydgf- loaded citrate-containing hydrogel was shown to significantly reduce scar formation and infarct size, increase wall thickness and neovascularization, and improve heart function. This bioactive injectable hydrogel-mediated combinatorial approach offers myriad advantages including potential adjustment of delivery rate and duration, improved therapeutic effect, and minimally invasive administration. Our rational design combining beneficial degradation product and controlled release of therapeutics provides inspiration toward the next generation of biomaterials aiming to revolutionize regenerative medicine.