Hydrogel Formation with Enzyme-Responsive Cyclic Peptides.
Hydrogel Formation with Enzyme-Responsive Cyclic Peptides.
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DOI：
10.1007/978-1-0716-1689-5_23
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发表时间：
2021-10
影响因子：
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通讯作者：
A. Carlini;Mary F Cassidy;N. Gianneschi
中科院分区：
文献类型：
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作者：
A. Carlini;Mary F Cassidy;N. Gianneschi
自组装肽是一类有趣的材料，通过可溶性结构的物理交联形成水凝胶，已被应用于组织工程支架和药物输送载体。为了通过微创输送实现这些组织模拟物的可行应用，它们的整体机械性能必须与当前的输送策略相兼容。然而，具有剪切稀化能力以及在剪切停止后重新组装的可注射汁液的生产在技术上可能是具有挑战性的。许多SAP要么在分娩过程中以高浓度堵塞大口径针/导管，要么在分娩后无法重新组装。在本章中，我们提供了一个详细的协议，用于酶响应性多肽水凝胶的拓扑控制，使用户能够获得这两个优点。这些材料被配制成空间受限的环肽孕激素，在注射给药过程中暂时扰乱自我组装，从而避免了针头和导管以及附近血管系统堵塞的问题。靶组织产生的酶对蛋白质的切割会导致孕激素的线性化和水凝胶。这种方法的范围体现在它们通过导管流动的能力，而不会堵塞，并在接触目标酶时激活凝胶。
Self-assembling peptides (SAPs), which form hydrogels through physical cross-linking of soluble structures, are an intriguing class of materials that have been applied as tissue engineering scaffolds and drug delivery vehicles. For feasible application of these tissue mimetics via minimally invasive delivery, their bulk mechanical properties must be compatible with current delivery strategies. However, injectable SAPs which possess shear-thinning capacity, as well as the ability to reassemble after cessation of shearing can be technically challenging to generate. Many SAPs either clog the high-gauge needle/catheter at high concentration during delivery or are incapable of reassembly following delivery. In this chapter, we provide a detailed protocol for topological control of enzyme-responsive peptide-based hydrogels that enable the user to access both advantages. These materials are formulated as sterically constrained cyclic peptide progelators to temporarily disrupt self-assembly during injection-based delivery, which avoids issues with clogging of needles and catheters as well as nearby vasculature. Proteolytic cleavage by enzymes produced at the target tissue induces progelator linearization and hydrogelation. The scope of this approach is demonstrated by their ability to flow through a catheter without clogging and activated gelation upon exposure to target enzymes.