Goktas Melis, Cinar Goksu, Orujalipoor Ilghar, Ide Semra, Tekinay Ayse B, Guler Mustafa O
†Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Biomacromolecules. 2015 Apr 13;16(4):1247-58. doi: 10.1021/acs.biomac.5b00041. Epub 2015 Mar 19.
Natural extracellular matrix (ECM) consists of complex signals interacting with each other to organize cellular behavior and responses. This sophisticated microenvironment can be mimicked by advanced materials presenting essential biochemical and physical properties in a synergistic manner. In this work, we developed a facile fabrication method for a novel nanofibrous self-assembled peptide amphiphile (PA) and poly(ethylene glycol) (PEG) composite hydrogel system with independently tunable biochemical, mechanical, and physical cues without any chemical modification of polymer backbone or additional polymer processing techniques to create synthetic ECM analogues. This approach allows noninteracting modification of multiple niche properties (e.g., bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for incorporation of bioactivity and porosity. Combining the self-assembled PA nanofibers with a chemically cross-linked polymer network simply by facile mixing followed by photopolymerization resulted in the formation of porous bioactive hydrogel systems. The resulting porous network can be functionalized with desired bioactive signaling epitopes by simply altering the amino acid sequence of the self-assembling PA molecule. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Therefore, nanofibrous self-assembled PA/PEG composite hydrogels reported in this work can provide new opportunities as versatile synthetic mimics of ECM with independently tunable biological and mechanical properties for tissue engineering and regenerative medicine applications. In addition, such systems could provide useful tools for investigation of how complex niche cues influence cellular behavior and tissue formation both in two-dimensional and three-dimensional platforms.
天然细胞外基质（ECM）由相互作用的复杂信号组成，以组织细胞行为和反应。这种复杂的微环境可以通过以协同方式呈现基本生化和物理特性的先进材料来模拟。在这项工作中，我们开发了一种简便的制造方法，用于制备新型纳米纤维自组装肽两亲物（PA）和聚乙二醇（PEG）复合水凝胶系统，该系统具有可独立调节的生化、机械和物理线索，无需对聚合物主链进行任何化学修饰或采用额外的聚合物加工技术来创建合成ECM类似物。这种方法允许对多种生态位特性（例如生物活性配体、硬度、孔隙率）进行非相互作用修饰，因为没有使用共价共轭方法来修饰PEG单体以纳入生物活性和孔隙率。通过简单混合然后光聚合将自组装PA纳米纤维与化学交联的聚合物网络相结合，导致形成多孔生物活性水凝胶系统。通过简单改变自组装PA分子的氨基酸序列，所得的多孔网络可以用所需的生物活性信号表位进行功能化。此外，通过改变PEG浓度可以精确控制复合系统的机械性能。因此，本文报道的纳米纤维自组装PA/PEG复合水凝胶可以作为多功能合成ECM模拟物提供新的机会，具有可独立调节的生物学和机械性能，用于组织工程和再生医学应用。此外，这样的系统可以为研究复杂的生态位线索如何在二维和三维平台上影响细胞行为和组织形成提供有用的工具。
