Boerman Marcel A, Roozen Edwin, Sánchez-Fernández María José, Keereweer Abraham R, Félix Lanao Rosa P, Bender Johan C M E, Hoogenboom Richard, Leeuwenburgh Sander C, Jansen John A, Van Goor Harry, Van Hest Jan C M
Institute for Molecules and Materials (IMM), Radboud University Nijmegen , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Department of Biomaterials, Radboudumc , Philip v. Leydenlaan 25, 6525 EX Nijmegen, The Netherlands.
Biomacromolecules. 2017 Aug 14;18(8):2529-2538. doi: 10.1021/acs.biomac.7b00683. Epub 2017 Jul 25.
In order to prevent hemorrhage during surgical procedures, a wide range of hemostatic agents have been developed. However, their efficacy is variable; hemostatic devices that use bioactive components to accelerate coagulation are dependent on natural sources, which limits reproducibility. Hybrid devices in which chain-end reactive poly(ethylene glycol) is employed as active component sometimes suffer from irregular cross-linking and dissolution of the polar PEG when blood flow is substantial. Herein, we describe a synthetic, nonbioactive hemostatic product by coating N-hydroxysuccinimide ester (NHS)-functional poly(2-oxazoline)s (POx-NHS) onto gelatin patches, which acts by formation of covalent cross-links between polymer, host blood proteins, gelatin and tissue to seal the wound site and prevent hemorrhage during surgery. We studied different process parameters (including polymer, carrier, and coating technique) in direct comparison with clinical products (Hemopatch and Tachosil) to obtain deeper understanding of this class of hemostatic products. In this work, we successfully prove the hemostatic efficacy of POx-NHS as polymer powders and coated patches both in vitro and in vivo against Hemopatch and Tachosil, demonstrating that POx-NHS are excellent candidate polymers for the development of next generation hemostatic patches.
为防止手术过程中出血，人们开发了多种止血剂。然而，它们的疗效各不相同；使用生物活性成分加速凝血的止血装置依赖于天然来源，这限制了可重复性。当血流充足时，以链端反应性聚乙二醇作为活性成分的混合装置有时会出现极性聚乙二醇交联不规则和溶解的问题。在此，我们描述了一种合成的非生物活性止血产品，它是通过将N-羟基琥珀酰亚胺酯（NHS）功能化的聚（2-恶唑啉）（POx-NHS）涂覆在明胶贴片上制成的，其作用是在聚合物、宿主血液蛋白、明胶和组织之间形成共价交联，以封闭伤口部位并防止手术期间出血。我们与临床产品（Hemopatch和Tachosil）直接比较研究了不同的工艺参数（包括聚合物、载体和涂覆技术），以更深入地了解这类止血产品。在这项工作中，我们成功证明了POx-NHS作为聚合物粉末和涂覆贴片在体外和体内相对于Hemopatch和Tachosil的止血效果，表明POx-NHS是开发下一代止血贴片的优秀候选聚合物。
