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非凝血障碍相关的仿生止血材料:从临床前模型到人体临床试验的完整研究故事。

Coagulopathy-independent, bioinspired hemostatic materials: A full research story from preclinical models to a human clinical trial.

机构信息

Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.

R&D Center, InnoTherapy Inc., Seoul, Republic of Korea.

出版信息

Sci Adv. 2021 Mar 24;7(13). doi: 10.1126/sciadv.abc9992. Print 2021 Mar.

Abstract

Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

摘要

自 1981 年首次报道海洋贻贝的水下粘附蛋白以来,已有大量研究报道了受贻贝启发的合成粘附聚合物。然而,它们都没有发展到适合人类的转化研究。在这里,我们报告了一种粘性多糖,它可以有效地促进从动物出血模型到首例人类肝切除术的止血。我们发现止血材料能立即生成一个屏障层,密封出血部位。屏障在几秒钟内通过与丰富的血浆蛋白的原位相互作用而形成。因此,只要患者血液中含有适当水平的血浆蛋白,即使在凝血功能障碍的情况下,也应该始终发生止血。迄今为止,尚未开发出足够的工具来阻止源于遗传疾病、慢性疾病或手术环境(如器官移植)的凝血功能障碍性出血。这里描述的贻贝启发式粘附化学为纤维蛋白胶在人类水平的生物医学应用提供了一种有用的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7990328/ade28757edde/abc9992-F1.jpg

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