Growth factor mediated assembly of cell receptor-responsive hydrogels
Growth factor mediated assembly of cell receptor-responsive hydrogels
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DOI：
10.1021/ja0680358
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发表时间：
2007-03-21
影响因子：
15
通讯作者：
Kiick, Kristi L.
中科院分区：
文献类型：
--
作者：
Yamaguchi, Nori;Zhang, Le;Kiick, Kristi L.
由蛋白质-多糖相互作用控制组装、机械响应和生物特性的材料的设计可以模拟生物环境，对适当的生物提示做出响应，并在许多生物医学应用中得到应用。在这里，我们报道了通过肝素功能化的STAR-PEG聚合物与治疗相关的肝素结合蛋白VEGF(血管内皮生长因子)的非共价相互作用组装水凝胶。通过激光镊子微观流变学评价了这些水凝胶的粘弹性能，以及血管内皮细胞生长因子在交联过程中的特异性。在VEGFR-2修饰的颗粒存在的情况下，通过水凝胶的放射测量分析表明，受体介导的血管内皮生长因子的传递伴随着水凝胶的侵蚀，这种相互作用的特异性在于，当与缺乏对血管内皮生长因子亲和力的蛋白质修饰的颗粒孵育时，水凝胶没有侵蚀。通过细胞增殖和活/死实验评估，从水凝胶中释放的血管内皮生长因子具有生物活性。这些结果表明，基于细胞和细胞外基质之间发生的配体-受体相互作用，有可能靶向输送生长因子和侵蚀水凝胶。其他二聚体肝素结合生长因子的治疗相关性，以及设计具有特定亲和力和治疗作用的多肽的机会，表明这些策略在生产生物医学应用的响应基质方面有更广泛的机会。
The design of materials in which assembly, mechanical response, and biological properties are controlled by protein-polysaccharide interactions may mimic the biological environment, be responsive to appropriate biological cues, and find use in many biomedical applications. Here we report the assembly of hydrogels via the noncovalent interaction of heparin-functionalized, star-PEG polymers and the therapeutically relevant, heparin-binding protein VEGF (vascular endothelial growth factor). The viscoelastic properties of these hydrogels, and the specificity of VEGF in crosslinking, were assessed via laser tweezer microrheology. The receptor-mediated delivery of VEGF, with concurrent erosion of the hydrogels, was indicated via radiometry assays of the hydrogels in the presence of VEGFR-2-modified particles, and the specificity of this interaction was indicated by a lack of erosion of the hydrogels when incubated with particles modified with a protein lacking affinity for VEGF. The VEGF delivered from the hydrogels is bioactive as assessed via cell proliferation and live/dead assays. These results indicate the potential for targeted delivery of growth factors and erosion of hydrogels on the basis of ligand-receptor interactions that occur between cells and the extracellular matrix. The therapeutic relevance of other dimeric heparin-binding growth factors, as well as opportunities for designing peptides with specific affinities and therapeutic action, suggests broader opportunities for these strategies in the production of responsive matrices for biomedical applications.