Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction
Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction
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DOI：
10.1038/s41467-019-09587-y
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发表时间：
2019-04-15
影响因子：
16.6
通讯作者：
Gianneschi, Nathan C.
中科院分区：
文献类型：
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作者：
Carlini, Andrea S.;Gaetani, Roberto;Gianneschi, Nathan C.
可注射的生物聚合物水凝胶作为促进心脏功能和预防心肌梗死（MI）后负性左心室（LV）重塑的支架已受到关注。然而，在临床前研究中测试的大多数水凝胶不是微创导管输送的候选者，因为材料粘度过大、凝胶化时间过快和/或对血液相容性和栓塞可能性的担忧。我们描述了一种平台技术，用于配制成空间受限的环肽的微生物材料，其自由流动以进行低阻力注射，并且当通过疾病相关酶线性化时快速组装成水凝胶。它们在体内的效用通过它们在大鼠模型中的MI部位流过注射器和凝胶的能力来证明。此外，合成功能化使这些材料能够流过心脏注射导管而不会堵塞，而不会损害血液相容性或细胞毒性。这些研究为开发用于向MI递送治疗性水凝胶的结构动态生物材料奠定了基础。
Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI.