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用于经导管动脉栓塞的丝弹性蛋白样蛋白聚合物栓塞的转化开发。

Translational Development of a Silk-Elastinlike Protein Polymer Embolic for Transcatheter Arterial Embolization.

机构信息

TheraTarget Inc., 36 S. Wasatch Dr., Salt Lake City, UT, 84112, USA.

Department of Biomedical Engineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT, 84112, USA.

出版信息

Macromol Biosci. 2022 Feb;22(2):e2100401. doi: 10.1002/mabi.202100401. Epub 2022 Jan 2.

DOI:10.1002/mabi.202100401
PMID:34978152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9007042/
Abstract

Locally blocking blood flow to tumors with embolic materials is the key to transcatheter arterial embolization for treating hepatocellular carcinoma. Current microparticle agents do not deeply penetrate target tissues and are compatible with a very limited selection of therapeutic agents. Silk-elastinlike protein polymers (SELPs) combine the solubility of elastin and the strength of silk to create an easily injected liquid embolic that transition into a solid depot amenable to loading with drugs, gene therapy agents, or biologics. SELP, injected as liquid solution, penetrates the vasculature before transitioning to a solid hydrogel. The objective of this manuscript is to evaluate SELP embolization, stability, and biocompatibility at 7-, 30-, and 90-day survival intervals in a porcine model. SELP embolics selectively block blood flow in the kidneys and livers, with no off-target infarctions. As assessed with angiography, SELP renal embolization exhibits decreasing persistence for the duration of the 90-day study period. There is an increased presence of microscopic SELP emboli in the renal setting, compared to Embosphere. Histologically scored inflammatory reactions to SELP are decreased in both the renal and hepatic implantations compared to Embosphere. In conclusion, a bioresorbable SELP liquid embolic system deeply penetrates target tissue and selectively embolizes blood vessels in vivo.

摘要

用栓塞材料局部阻断肿瘤血流是经导管动脉栓塞治疗肝细胞癌的关键。目前的微粒剂不能深入穿透靶组织,并且与非常有限的治疗剂兼容。丝弹性蛋白样蛋白聚合物(SELPs)结合了弹性蛋白的溶解性和丝的强度,形成了一种易于注射的液体栓塞剂,可转变为固体储存库,可加载药物、基因治疗剂或生物制剂。SELPs 作为液体溶液注射,在转变为固体水凝胶之前穿透血管。本文的目的是在猪模型中评估 SELP 栓塞、稳定性和生物相容性在 7、30 和 90 天存活期的情况。SELP 栓塞剂选择性地阻断肾脏和肝脏的血流,没有非靶组织梗塞。通过血管造影评估,SELP 肾栓塞在 90 天研究期间的持续时间内持续时间逐渐减少。与 Embosphere 相比,在肾脏中,SELP 的微观栓塞物的存在增加。与 Embosphere 相比,SELP 在肾和肝植入物中的组织学评分炎症反应减少。总之,生物可吸收的 SELP 液体栓塞系统可深入穿透靶组织,并在体内选择性地栓塞血管。

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