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基于明胶和微生物转谷氨酰胺酶的仿生密封剂:初步体内研究

Biomimetic sealant based on gelatin and microbial transglutaminase: an initial in vivo investigation.

作者信息

Liu Yi, Kopelman Doron, Wu Li-Qun, Hijji Karam, Attar Ishay, Preiss-Bloom Orahn, Payne Gregory F

机构信息

Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2009 Oct;91(1):5-16. doi: 10.1002/jbm.b.31368.

DOI:10.1002/jbm.b.31368
PMID:19360881
Abstract

The potential of an in situ gel-forming adhesive was examined as a hemostatic surgical sealant. The gel-forming mechanism for this adhesive mimics the last stages of blood coagulation but uses nonblood proteins. Specifically, gelatin is used as the structural protein and a calcium-independent microbial transglutaminase (mTG) is used as the crosslinking enzyme. In vitro burst pressure tests with porcine skin demonstrate that the gelatin-mTG adhesive forms a gel within 30 min under moist conditions and this gel can restrain pressures of 200 mmHg. In vivo tests with a rat liver wound model showed that the gelatin-mTG adhesive achieves complete hemostasis in 2.5 min and the gel (i.e., the biomimetic clot) offers substantial adhesive and cohesive strength. Complete hemostasis was also observed in 2.5 min after the gelatin-mTG adhesive was applied to a briskly bleeding rat femoral artery wound. In a large animal porcine model, a femoral artery wound that resulted in extensive bleeding was sealed in 4 min by (i) clamping the artery for temporary hemostasis, (ii) removing excess blood, and (iii) applying the gelatin-mTG adhesive. Thus, the biomimetic gelatin-mTG adhesive may provide a simple, safe, and cost-effective surgical sealant.

摘要

研究了一种原位凝胶形成粘合剂作为止血手术密封剂的潜力。这种粘合剂的凝胶形成机制模仿血液凝固的最后阶段,但使用非血液蛋白质。具体而言,明胶用作结构蛋白,钙非依赖性微生物转谷氨酰胺酶(mTG)用作交联酶。用猪皮进行的体外爆破压力测试表明,明胶-mTG粘合剂在潮湿条件下30分钟内形成凝胶,该凝胶可承受200 mmHg的压力。用大鼠肝伤口模型进行的体内测试表明,明胶-mTG粘合剂在2.5分钟内实现完全止血,并且该凝胶(即仿生凝块)具有相当大的粘附力和内聚力。将明胶-mTG粘合剂应用于快速出血的大鼠股动脉伤口后,在2.5分钟内也观察到完全止血。在大型动物猪模型中,通过(i)夹住动脉进行临时止血,(ii)清除多余血液,以及(iii)应用明胶-mTG粘合剂,在4分钟内封闭了导致大量出血的股动脉伤口。因此,仿生明胶-mTG粘合剂可能提供一种简单、安全且经济高效的手术密封剂。

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