首页> 美国卫生研究院文献>Advanced Science >A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials
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A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials

机译:一种朝向血管生成的仿生方法:重组表达的人PERCENAN的域V是一种生物活性分子促进植入生物材料的血管生成和血管化

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摘要

Angiogenic therapy involving delivery of pro‐angiogenic growth factors to stimulate new blood vessel formation in ischemic disease is promising but has seen limited clinical success due to issues associated with the need to deliver supra‐physiological growth factor concentrations. Bio‐inspired growth factor delivery utilizing the native growth factor signaling roles of the extracellular matrix proteoglycans has the potential to overcome many of the drawbacks of angiogenic therapy. In this study, the potential of the recombinantly expressed domain V (rDV) of human perlecan is investigated as a means of promoting growth factor signaling toward enhanced angiogenesis and vascularization of implanted biomaterials. rDV is found to promote angiogenesis in established in vitro and in vivo angiogenesis assays by potentiating endogenous growth factor signaling via its glycosaminoglycan chains. Further, rDV is found to potentiate fibroblast growth factor 2 (FGF2) signaling at low concentrations that in the absence of rDV are not biologically active. Finally, rDV immobilized on 3D porous silk fibroin biomaterials promotes enhanced vascular ingrowth and integration of the implanted scaffolds with the surrounding tissue. Together, these studies demonstrate the important role of this biologically active perlecan fragment and its potential in the treatment of ischemia in both native and bioengineered tissues.
机译:涉及促进血管生成增长因子以刺激缺血性疾病的新血管形成的血管生成治疗是有前途的,但由于与需要提供同上生理生长因子浓度相关的问题,临床成功有限。利用细胞外基质蛋白多糖的天然生长因子信号传导作用的生物启发生长因子递送具有克服血管生成治疗的许多缺点的可能性。在该研究中,研究了人普萘兰的重组表达结构域V(RDV)的潜力作为促进增强血管生成和植入生物材料的增强血管生成和血管化的手段。发现RDV通过通过其糖胺聚糖链增强内源生长因子信号传导,促进在体外和体内血管生成测定中促进血管生成。此外,发现RDV在不存在RDV的低浓度下使RDV产生成纤维细胞生长因子2(FGF2)信号传导不是生物学活性的。最后,RDV固定在3D多孔丝素蛋白生物材料上促进了增强的血管生长和与周围组织的植入支架整合。这些研究在一起表明了这种生物活性的PERECAN片段的重要作用及其在天然和生物内组织中治疗缺血的潜力。

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