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一种可注射的剪切稀化生物材料,用于血管内栓塞。

An injectable shear-thinning biomaterial for endovascular embolization.

机构信息

Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Sci Transl Med. 2016 Nov 16;8(365):365ra156. doi: 10.1126/scitranslmed.aah5533.

Abstract

Improved endovascular embolization of vascular conditions can generate better patient outcomes and minimize the need for repeat procedures. However, many embolic materials, such as metallic coils or liquid embolic agents, are associated with limitations and complications such as breakthrough bleeding, coil migration, coil compaction, recanalization, adhesion of the catheter to the embolic agent, or toxicity. Here, we engineered a shear-thinning biomaterial (STB), a nanocomposite hydrogel containing gelatin and silicate nanoplatelets, to function as an embolic agent for endovascular embolization procedures. STBs are injectable through clinical catheters and needles and have hemostatic activity comparable to metallic coils, the current gold standard. In addition, STBs withstand physiological pressures without fragmentation or displacement in elastomeric channels in vitro and in explant vessels ex vivo. In vitro experiments also indicated that STB embolization did not rely on intrinsic thrombosis as coils did for occlusion, suggesting that the biomaterial may be suitable for use in patients on anticoagulation therapy or those with coagulopathy. Using computed tomography imaging, the biomaterial was shown to fully occlude murine and porcine vasculature in vivo and remain at the site of injection without fragmentation or nontarget embolization. Given the advantages of rapid delivery, in vivo stability, and independent occlusion that does not rely on intrinsic thrombosis, STBs offer an alternative gel-based embolic agent with translational potential for endovascular embolization.

摘要

改良的血管内栓塞治疗可以改善患者的预后,减少重复治疗的需求。然而,许多栓塞材料,如金属线圈或液体栓塞剂,都存在局限性和并发症,如突破性出血、线圈迁移、线圈压实、再通、导管与栓塞剂粘连或毒性。在这里,我们设计了一种剪切稀化生物材料(STB),这是一种含有明胶和硅酸盐纳米片的纳米复合水凝胶,可用作血管内栓塞治疗的栓塞剂。STB 可通过临床导管和针头注射,其止血活性可与目前的金标准——金属线圈相媲美。此外,STB 在体外弹性通道和离体血管中不会发生碎片化或移位,可耐受生理压力。体外实验还表明,STB 栓塞并不依赖于线圈那样的固有血栓形成来实现闭塞,这表明该生物材料可能适用于正在接受抗凝治疗或存在凝血功能障碍的患者。通过计算机断层扫描成像,该生物材料在体内完全闭塞了小鼠和猪的血管,并且在注射部位没有发生碎片化或非目标栓塞。鉴于快速输送、体内稳定性和不依赖固有血栓形成的独立闭塞等优势,STB 为血管内栓塞提供了一种替代的基于凝胶的栓塞剂,具有转化应用的潜力。

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