State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, Jiangsu, 211189, P. R. China.
Adv Healthc Mater. 2024 Feb;13(5):e2302209. doi: 10.1002/adhm.202302209. Epub 2023 Nov 16.
Thrombin, a coagulation-inducing protease, has long been used in the hemostatic field. During the past decades, many other therapeutic uses of thrombin have been developed. For instance, burn treatment, pseudoaneurysm therapy, wound management, and tumor vascular infarction (or tumor vasculature blockade therapy) can all utilize the unique and powerful function of thrombin. Based on their therapeutic effects, many thrombin-associated products have been certificated by the Food and Drug Administration, including bovine thrombin, human thrombin, recombinant thrombin, fibrin glue, etc. Besides, several thrombin-based drugs are currently undergoing clinical trials. In this article, the therapeutic uses of thrombin (from the initial hemostasis to the latest cancer therapy), the commercially available drugs associated with thrombin, and the pros and cons of thrombin-based therapeutics (e.g., adverse immune responses related to bovine thrombin, thromboinflammation, and vasculogenic "rebounds") are summarized. Further, the current challenges and possible future research directions of thrombin-incorporated biomaterials and therapies are discussed. It is hoped that this review may provide a valuable reference for researchers in this field and help them to design safer and more effective thrombin-based drugs for fighting against various intractable diseases.
凝血酶是一种促凝血的蛋白酶，长期以来一直用于止血领域。在过去的几十年中，人们已经开发出了许多其他的凝血酶治疗用途。例如，烧伤治疗、假性动脉瘤治疗、伤口管理和肿瘤血管梗死（或肿瘤血管阻断治疗）都可以利用凝血酶的独特而强大的功能。基于其治疗效果，许多与凝血酶相关的产品已获得美国食品和药物管理局的认证，包括牛凝血酶、人凝血酶、重组凝血酶、纤维蛋白胶等。此外，目前还有几种基于凝血酶的药物正在进行临床试验。本文总结了凝血酶的治疗用途（从最初的止血到最新的癌症治疗）、与凝血酶相关的市售药物，以及基于凝血酶的治疗方法的优缺点（例如，与牛凝血酶相关的不良免疫反应、血栓炎症和血管生成“反弹”）。此外，还讨论了当前凝血酶结合生物材料和治疗方法所面临的挑战和未来可能的研究方向。希望这篇综述能为该领域的研究人员提供有价值的参考，并帮助他们设计出更安全、更有效的基于凝血酶的药物，以对抗各种难治性疾病。
