The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hindlimb ischemia model
The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hindlimb ischemia model
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DOI：
10.1016/j.biomaterials.2010.02.026
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发表时间：
2010-06-01
期刊：
影响因子：
14
通讯作者：
Cohen, Smadar
中科院分区：
文献类型：
--
作者：
Ruvinov, Emil;Leor, Jonathan;Cohen, Smadar
通过使用活性脱细胞生物材料来增强组织的自我修复是再生医学的主要目标之一。我们现在描述的特点，可注射的藻酸盐生物材料的设计亲和结合肝素结合蛋白，并释放它们的速度反映了他们的协会常数藻酸盐硫酸盐。肝细胞生长因子（HGF）与藻酸盐-硫酸盐的相互作用导致保护因子免受蛋白水解，如胰蛋白酶消化后的质谱分析所示。当HGF/藻酸盐-硫酸盐生物缀合物掺入藻酸盐水凝胶时。HGF的释放持续了3倍，与未改性水凝胶的释放速率相比。释放的因子保留活性，如通过其诱导ERK 1/2活化和在大鼠新生心肌细胞培养中提供细胞保护所示。在体内，注射形式的亲和结合藻酸盐系统延长了10倍，与盐水处理组相比，心肌梗死后立即递送时，HGF在心肌组织中的保留。在严重的小鼠后肢缺血模型中，从亲和结合系统递送HGF改善组织血液灌注并诱导成熟血管网络形成。亲和结合系统的治疗功效以及其易于通过注射递送，为这种生物活性生物材料策略在心血管修复中的潜在用途提供了概念验证。(C)2010爱思唯尔有限公司保留所有权利。
Enhancing tissue self-repair through the use of active acellular biomaterials is one of the main goals of regenerative medicine. We now describe the features of an injectable alginate biomaterial designed to affinity-bind heparin binding proteins and release them at a rate reflected by their association constant to alginate-sulfate. The interactions of hepatocyte growth factor (HGF) with alginate-sulfate resulted in factor protection from proteolysis, as shown by mass spectroscopy analysis after trypsin digestion. When the HGF/alginate-sulfate bioconjugate was incorporated into alginate hydrogel. HGF release was sustained by a factor of 3, as compared to the release rate from non-modified hydrogel. The released factor retained activity, as shown by its induction of ERK1/2 activation and affording cytoprotection in rat neonatal cardiomyocyte cultures. In vivo, an injectable form of the affinity-binding alginate system extended by 10-fold, as compared to a saline-treated group, retention of HGF in myocardial tissue when delivered immediately after myocardial infarction. In a severe murine hindlimb ischemia model, HGF delivery from the affinity-binding system improved tissue blood perfusion and induced mature blood vessel network formation. The therapeutic efficacy of the affinity-binding system, as well as its ease of delivery by injection, provides a proof-of-concept for the potential use of this bioactive biomaterial strategy in cardiovascular repair. (C) 2010 Elsevier Ltd. All rights reserved.