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用于膀胱阴道瘘的再生不可混溶生物胶的临床前评估。

Preclinical evaluation of a regenerative immiscible bioglue for vesico-vaginal fistula.

机构信息

Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, South Korea; Research Center for Bio-Based Chemistry, Korea Research Institute of Chemical Technology, Ulsan 44429, South Korea.

Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea.

出版信息

Acta Biomater. 2021 Apr 15;125:183-196. doi: 10.1016/j.actbio.2021.02.037. Epub 2021 Feb 27.

DOI:10.1016/j.actbio.2021.02.037
PMID:33652167
Abstract

Currently, there are no clinically available tissue adhesives that work effectively in the fluid-rich and highly dynamic environments of the human body, such as the urinary system. This is especially relevant to the management of vesico-vaginal fistula, and developing a high-performance tissue adhesive for this purpose could vastly expand urologists' surgical repertoire and dramatically reduce patient discomfort. Herein, we developed a water-immiscible mussel protein-based bioadhesive (imWIMBA) with significantly improved properties in all clinical respects, allowing it to achieve rapid and strong underwater adhesion with tunable rheological properties. We evaluated in vivo potential of imWIMBA for sealing thermally injured fistula tracts between the bladder and vagina. Importantly, the use of imWIMBA in the presence of prolonged bladder drainage resulted in perfect closure of the vesico-vaginal fistula in operated pigs. Thus, imWIMBA could be successfully used for many surgical applications and improve treatment efficacy when combined with conventional surgical methods. STATEMENT OF SIGNIFICANCE: Vesico-vaginal fistula (VVF) is an abnormal opening between the bladder and the vagina, which is a stigmatized disease in many developing countries. Leakage of urine into internal organs can induce serious complications and delay wound repair. Conventional VVF treatment requires skillful suturing to provide a tension-free and watertight closure. In addition, there is no clinically approved surgical glue that works in wet and highly dynamic environments such as the urinary system. In this work, for potential clinical VVF closure and regeneration, we developed an advanced immiscible mussel protein-based bioglue with fast, strong, wet adhesion and tunable rheological properties. This regenerative immiscible bioglue could be successfully used for sealing fistulas and further diverse surgical applications as an adjuvant for conventional suture methods.

摘要

目前,还没有在人体富液和高度动态环境中(如泌尿系统)有效发挥作用的临床可用的组织粘合剂。这对于膀胱阴道瘘的处理尤其重要,为此开发高性能的组织粘合剂可以极大地扩展泌尿科医生的手术范围,并显著减轻患者的不适。在此,我们开发了一种不溶于水的贻贝类蛋白基生物粘合剂(imWIMBA),在所有临床方面均具有显著改善的性能,使其能够实现快速、强力的水下粘附,并具有可调节的流变性能。我们评估了 imWIMBA 用于密封膀胱和阴道之间热损伤瘘道的体内潜力。重要的是,在长时间膀胱引流的情况下使用 imWIMBA 可导致手术猪的膀胱阴道瘘完全闭合。因此,imWIMBA 可成功用于多种手术应用,并与传统手术方法结合使用时可提高治疗效果。

意义

膀胱阴道瘘(VVF)是膀胱和阴道之间的异常开口,在许多发展中国家,这是一种耻辱性疾病。尿液泄漏到内部器官会引起严重的并发症并延迟伤口愈合。传统的 VVF 治疗需要熟练的缝合技术,以提供无张力和防水的闭合。此外,在泌尿系统等湿且高度动态的环境中,尚无临床批准的手术胶。在这项工作中,为了潜在的临床 VVF 闭合和再生,我们开发了一种先进的不混溶贻贝类蛋白基生物胶,具有快速、强力、湿粘附和可调节流变性能。这种再生不混溶生物胶可成功用于密封瘘管和进一步的各种手术应用,作为传统缝合方法的辅助手段。

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