Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons.

Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons.
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DOI:
10.1021/acsbiomaterials.7b00347
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发表时间:
2017-09-11
影响因子:
5.8
通讯作者:
Stupp SI
Stupp SI
中科院分区:
工程技术2区
文献类型:
--
作者:
Rubert Pérez CM;Álvarez Z;Chen F;Aytun T;Stupp SI

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成纤维细胞生长因子(FGF-2)是一种多功能的生长因子,在不同的组织和器官中具有多效性。特别地,FGF-2在血管生成中具有特殊作用,血管生成是发育、伤口愈合、细胞存活和分化中的重要过程。因此,在治疗性生物材料中掺入生物制剂如FGF-2是产生血管生成生物活性以修复由创伤或由年龄和/或疾病引起的并发症引起的受损组织的潜在策略。然而,使用生长因子作为治疗剂可能是昂贵的,并且由于从靶向部位的快速清除而不总是带来有效的组织修复。另一种选择是稳定的超分子纳米结构,具有激活FGF-2受体的能力,也可以组装成可输送到组织的支架。我们在这里报告的肽两亲物,纳入肽已知激活FGF-2受体和肽结构域,驱动其自组装成超分子纳米带。这些FGF 2-PA纳米带显示出在体外增加人脐静脉内皮细胞(HUVECs)的增殖和迁移的能力,其程度与某些浓度的天然FGF-2蛋白相同。我们通过跟踪下游信号效应物如ERK 1/2和pH 3的磷酸化,证实了这种活性对FGFR 1信号通路是特异性的。这些结果表明FGF 2-PA纳米带在激活FGF-2信号通路方面的特异性及其作为超分子支架的潜在应用,该支架可在体内用作天然FGF-2蛋白包封和递送的替代方案。
Fibroblast growth factor (FGF-2) is a multifunctional growth factor that has pleiotropic effects in different tissues and organs. In particular, FGF-2 has a special role in angiogenesis, an important process in development, wound healing, cell survival, and differentiation. Therefore, incorporating biological agents like FGF-2 within therapeutic biomaterials is a potential strategy to create angiogenic bioactivity for the repair of damaged tissue caused by trauma or complications that arise from age and/or disease. However, the use of growth factors as therapeutic agents can be costly and does not always bring about efficient tissue repair due to rapid clearance from the targeted site. An alternative would be a stable supramolecular nanostructure with the capacity to activate the FGF-2 receptor that can also assemble into a scaffold deliverable to tissue. We report here on peptide amphiphiles that incorporate a peptide known to activate the FGF-2 receptor and peptide domains that drive its self-assembly into supramolecular nanoribbons. These FGF2-PA nanoribbons displayed the ability to increase the proliferation and migration of the human umbilical vein endothelial cells (HUVECs) in vitro to the same extent as the native FGF-2 protein at certain concentrations. We confirmed that this activity was specific to the FGFR1 signaling pathway by tracking the phosphorylation of downstream signaling effectors such ERK1/2 and pH3. These results indicated the specificity of FGF2-PA nanoribbons in activating the FGF-2 signaling pathway and its potential application as a supramolecular scaffold that can be used in vivo as an alternative to the encapsulation and delivery of the native FGF-2 protein.
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