Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Biomaterials. 2010 Jun;31(16):4573-82. doi: 10.1016/j.biomaterials.2010.02.026. Epub 2010 Mar 5.
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.
通过使用活性去细胞生物材料来增强组织的自我修复能力是再生医学的主要目标之一。我们现在描述了一种可注射藻酸盐生物材料的特性，该材料旨在亲和结合肝素结合蛋白，并根据其与藻酸盐硫酸盐的结合常数以一定的速率释放它们。 肝细胞生长因子（HGF）与藻酸盐硫酸盐的相互作用导致因子免受蛋白水解的保护，这可以通过胰蛋白酶消化后的质谱分析来证明。当 HGF/藻酸盐硫酸盐生物缀合物被掺入藻酸盐水凝胶中时，与非修饰水凝胶的释放速率相比，HGF 的释放速度延长了 3 倍。释放的因子保持活性，因为它可以诱导 ERK1/2 激活并为大鼠新生心肌细胞培养物提供细胞保护。在体内，与盐水处理组相比，亲和结合藻酸盐系统的可注射形式延长了 10 倍，在心肌梗死后立即给药时，心肌组织中 HGF 的保留。在严重的小鼠后肢缺血模型中，亲和结合系统中 HGF 的递送改善了组织血液灌注并诱导了成熟血管网络的形成。亲和结合系统的治疗效果及其通过注射进行递送的简便性为该生物活性生物材料策略在心血管修复中的潜在应用提供了概念验证。
