Slow and sustained release of active cytokines from self-assembling peptide scaffolds
Slow and sustained release of active cytokines from self-assembling peptide scaffolds
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DOI：
10.1016/j.jconrel.2010.04.026
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发表时间：
2010-08-03
影响因子：
10.8
通讯作者：
Zhang, Shuguang
中科院分区：
文献类型：
--
作者：
Gelain, Fabrizio;Unsworth, Larry D.;Zhang, Shuguang
控制细胞微环境被认为是成功应用生物材料用于再生医学策略的关键。自组装肽被证明是一个有前途的平台，用于各种再生医学应用。具体而言，RADA 16-I自组装肽已成功用于3D细胞培养、加速伤口愈合和神经修复。了解蛋白质在这种纳米结构系统中流动并最终从其中释放的基本机制是控制细胞活性的一个关键方面;文献中基本上缺乏研究。在这里，我们报告说，设计师自组装肽支架促进缓慢和持续释放的活性细胞因子，是非常相关的再生医学的许多领域。此外，在RADA 16-I和两种不同的RADA 16-I形成肽内观察到人β FGF、VEGF和BDNF存在多种扩散机制，所述肽具有位于C末端的净正电荷或负电荷。在某些情况下，在分子水平上观察到两个扩散分子群体：一个在溶剂中完全扩散，另一个表现出受阻的流动性。结果表明，蛋白质的流动性受到抑制的蛋白质和肽纳米纤维之间的物理阻碍和电荷诱导的相互作用。此外，使用成体神经干细胞（NSC）的测定用于评估长达三周的活性细胞因子（β FGF）的功能性释放。我们的研究结果不仅为自组装肽支架的长期分子释放提供了证据，而且为临床应用的大量缓慢分子释放策略提供了灵感。(c)2010爱思唯尔有限公司版权所有。
Controlling the cellular microenvironment is thought to be critical for the successful application of biomaterials for regenerative medicine strategies. Self-assembling peptides are proving to be a promising platform for a variety of regenerative medicine applications. Specifically, RADA16-I self-assembling peptides have been successfully used for 3D cell culture, accelerated wound healing, and nerve-repair. Understanding the fundamental mechanisms for protein mobility within, and ultimately release from, this nanostructured system is a critical aspect for controlling cellular activity; studies which are largely lacking within the literature. Herein, we report that designer self-assembling peptide scaffolds facilitate slow and sustained release of active cytokines that are extremely relevant to many areas of regenerative medicine. In addition, multiple diffusive mechanisms are observed to exist for human beta FGF, VEGF and BDNF within RADA16-I and two different RADA16-I nanofiber forming peptides with net positive or negative charges located at the C-terminus. In some cases, two populations of diffusing molecules are observed at the molecular level: one diffusing fully within the solvent, and another that exhibits hindered mobility. Results suggest that protein mobility is inhibited by both physical hinderances and charge induced interactions between the protein and peptide nanofibers. Moreover, assays using adult neural stem cells (NSCs) are employed to assess the functional release of active cytokine (beta FGF) up to three weeks. Our results not only provide evidence for long-term molecular release from self-assembling peptide scaffolds but also inspiration for a plethora of slow molecular release strategies for clinical applications. (c) 2010 Elsevier B.V. All rights reserved.