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用于心肌细胞培养和注射的可光交联水凝胶。

Photocrosslinkable hydrogel for myocyte cell culture and injection.

作者信息

Yeo Yoon, Geng Wenliang, Ito Taichi, Kohane Daniel S, Burdick Jason A, Radisic Milica

机构信息

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2007 May;81(2):312-22. doi: 10.1002/jbm.b.30667.

Abstract

Conventional treatment options for myocardial infarction are limited by the inability of mature myocardium to regenerate after injury. Although functional improvements after injection of cells and growth factors have been demonstrated, the clinical utility of this procedure has been hampered by poor cell localization, low survival, and rapid clearance of injected growth factors. The main objective of this study was to evaluate the applicability of a hydrogel, based on photocrosslinkable chitosan and acryloyl-poly(ethylene glycol)-RGDS (Az-chitosan/Acr-PEG-RGD) for myocyte cell culture and myocardial injection. Chitosan was modified with photoreactive azidobenzoic acid and Acr-PEG-RGD was synthesized by reacting YRGDS with an equimolar amount of acryloyl-PEG-N-hydroxysuccinimide. For injection and encapsulation each polymer was dissolved in Di-H(2)O (pH 6.4), the solutions were mixed and crosslinked by UV application (4 mW/cm(2)). C2C12 myoblasts proliferated and differentiated on hydrogels containing 5 mM RGD but not on the pure photocrosslinked chitosan. In vitro, the crosslinked hydrogels retained 80% of encapsulated VEGF for 24 days. Live/dead staining of neonatal rat cardiomyocytes encapsulated into Az-chitosan/Acr-PEG-RGD hydrogels indicated high cell viability upon UV crosslinking. Ex vivo, we localized the hydrogel on the surface and in the ventricle wall of an adult rat heart by brief (2 min) UV light application.

摘要

心肌梗死的传统治疗选择受到成熟心肌损伤后无法再生的限制。尽管已证明注射细胞和生长因子后功能有所改善,但该方法的临床应用受到细胞定位不佳、存活率低以及注射的生长因子快速清除的阻碍。本研究的主要目的是评估一种基于光交联壳聚糖和丙烯酰基聚乙二醇-RGDS(Az-壳聚糖/Acr-PEG-RGD)的水凝胶在心肌细胞培养和心肌注射中的适用性。壳聚糖用光反应性叠氮苯甲酸进行修饰,Acr-PEG-RGD通过使YRGDS与等摩尔量的丙烯酰基聚乙二醇-N-羟基琥珀酰亚胺反应合成。为了进行注射和包封,将每种聚合物溶解在去离子水(pH 6.4)中,混合溶液并通过紫外线照射(4 mW/cm²)进行交联。C2C12成肌细胞在含有5 mM RGD的水凝胶上增殖并分化,但在纯光交联壳聚糖上则不然。在体外,交联水凝胶在24天内保留了80%包封的血管内皮生长因子(VEGF)。对包封在Az-壳聚糖/Acr-PEG-RGD水凝胶中的新生大鼠心肌细胞进行活/死染色,结果表明紫外线交联后细胞活力较高。在体外,通过短暂(2分钟)紫外线照射,我们将水凝胶定位在成年大鼠心脏的表面和心室壁上。

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