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一种儿茶酚生物黏附剂,用于快速止血和治疗创伤性内脏器官和大血管。

A catechol bioadhesive for rapid hemostasis and healing of traumatic internal organs and major arteries.

机构信息

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, Shandong, PR China; Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, Shandong, PR China.

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, Shandong, PR China; School of Basic Medicine, College of Medicine, Qingdao University, Qingdao, 266071, Shandong, PR China.

出版信息

Biomaterials. 2022 Dec;291:121908. doi: 10.1016/j.biomaterials.2022.121908. Epub 2022 Nov 10.

Abstract

Uncontrolled hemorrhage caused by trauma to internal organs or major arteries poses critical threats to lives. However, rapid hemostasis followed by tissue repair remains an intractable challenge in surgery owing to the lack of ideal internal-use adhesives that can achieve fast and robust wet adhesion and accelerate wound healing. Herein, we develop a robust hemostatic bioadhesive (CAGA) from novel highly-branched aminoethyl gelatin with end-grafted abundant catechol (Gel-AE-Ca). The unique chemical structure of Gel-AE-Ca makes CAGA capable of gelling on wet tissues via synergetic cross-linking of catechol-Fe chelation and horseradish peroxidase (HRP)/HO-triggered covalent bonds using a dual-channel needle, meeting the key demands of internal medical applications (e.g., instant and strong wet adhesion, injectability, biocompatibility, self-healing, stretching flexibility, infection resistance, and proper biodegradability). It exhibits rapid gelation within 10 s and robust wet tissue adhesion up to 115.0 ± 13.1 kPa of shear strength and 245.0 ± 33.8 mm Hg of sealing strength. In vivo trials demonstrate that CAGA can not only effectively seal anastomosis of the carotid artery, but achieve rapid hemostasis on the sites of liver incisions and penetrating cardiac wounds within 10 s. The wound closure by CAGA and its timely biodegradation promote wound healing of the vital organs.

摘要

创伤导致的内部器官或主要动脉出血是对生命的严重威胁。然而,由于缺乏理想的内用黏合剂来实现快速和牢固的湿黏附并加速伤口愈合,因此手术后快速止血和组织修复仍然是一个棘手的挑战。在此,我们用末端接枝大量儿茶酚的新型高度支化的氨基乙基明胶(Gel-AE-Ca)开发了一种强大的止血生物黏合剂(CAGA)。Gel-AE-Ca 的独特化学结构使 CAGA 能够通过儿茶酚-Fe 螯合和辣根过氧化物酶(HRP)/HO 触发的共价键的协同交联在湿组织上形成凝胶,使用双通道针满足内部医疗应用的关键需求(例如,即时和强大的湿黏附、可注射性、生物相容性、自修复、拉伸灵活性、抗感染性和适当的生物降解性)。它在 10 秒内迅速凝胶化,并具有强大的湿组织黏附力,剪切强度高达 115.0±13.1kPa,密封强度高达 245.0±33.8mmHg。体内试验表明,CAGA 不仅可以有效地密封颈动脉吻合口,而且可以在 10 秒内迅速止血肝脏切口和穿透性心脏伤口。CAGA 的伤口闭合及其及时的生物降解促进了重要器官的伤口愈合。

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