Overstreet Derek J, Lee Elizabeth J, Pal Amrita, Vernon Brent L
School of Biological and Health Systems Engineering, Center for Interventional Biomaterials, Arizona State University, Tempe, Arizona, USA.
J Biomed Mater Res B Appl Biomater. 2022 Aug;110(8):1911-1921. doi: 10.1002/jbm.b.35048. Epub 2022 Mar 9.
Endovascular embolization of cerebral aneurysms is a common approach for reducing the risk of often-fatal hemorrhage. However, currently available materials used to occlude these aneurysms provide incomplete filling (coils) or require a complicated, time-consuming delivery procedure (solvent-exchange precipitating polymers). The objective of this work was to develop an easily deliverable in situ forming hydrogel that can occlude the entire volume of an aneurysm. The hydrogel is formed by mixing a solution of a temperature-responsive polymer containing pendent thiol groups (poly(NIPAAm-co-cysteamine) or poly(NIPAAm-co-cysteamine-co-JAAm)) with a solution of poly(ethylene glycol) diacrylate (PEGDA). Incorporation of hydrophilic grafts of polyetheramine acrylamide (JAAm) in the temperature-responsive polymer caused weaker physical crosslinking, facilitated faster and more complete chemical crosslinking, and increased gel swelling. One formulation (30 wt % PNCJ20 + PEGDA) could be delivered for over 220 s after mixing, formed a strong and elastic hydrogel (G' > 6000 Pa) within 30 min and once set, maintained its shape and volume in a model aneurysm under flow. This gel represents a promising candidate water-based material utilizing both physical and chemical crosslinking that warrants further investigation as an embolic agent for saccular aneurysms.
脑动脉瘤的血管内栓塞是降低常导致致命性出血风险的常用方法。然而，目前用于闭塞这些动脉瘤的材料要么提供不完全填充（线圈），要么需要复杂、耗时的输送过程（溶剂交换沉淀聚合物）。这项工作的目的是开发一种易于输送的原位形成水凝胶，它能够闭塞动脉瘤的整个容积。该水凝胶通过将含有侧链硫醇基团的温度响应聚合物（聚（N - 异丙基丙烯酰胺 - 共 - 半胱胺）或聚（N - 异丙基丙烯酰胺 - 共 - 半胱胺 - 共 - 聚醚胺丙烯酰胺））溶液与聚乙二醇二丙烯酸酯（PEGDA）溶液混合形成。在温度响应聚合物中引入聚醚胺丙烯酰胺（JAAm）的亲水性接枝物会导致较弱的物理交联，促进更快、更完全的化学交联，并增加凝胶溶胀。一种配方（30 wt% PNCJ20 + PEGDA）在混合后可输送超过220秒，在30分钟内形成强而有弹性的水凝胶（G' > 6000 Pa），一旦凝固，在流动的模型动脉瘤中保持其形状和体积。这种凝胶代表了一种有前途的利用物理和化学交联的水基材料，作为囊状动脉瘤的栓塞剂值得进一步研究。
