Dankers Patricia Y W, Harmsen Martin C, Brouwer Linda A, van Luyn Marja J A, Meijer E W
Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, PO Box 513, NL-5600 MB Eindhoven, The Netherlands.
Nat Mater. 2005 Jul;4(7):568-74. doi: 10.1038/nmat1418. Epub 2005 Jun 19.
Bioactive polymeric scaffolds are a prerequisite for the ultimate formation of functional tissues. Here, we show that supramolecular polymers based on quadruple hydrogen bonding ureido-pyrimidinone (UPy) moieties are eminently suitable for producing such bioactive materials owing to their low-temperature processability, favourable degradation and biocompatible behaviour. Particularly, the reversible nature of the hydrogen bonds allows for a modular approach to gaining control over cellular behaviour and activity both in vitro and in vivo. Bioactive materials are obtained by simply mixing UPy-functionalized polymers with UPy-modified biomolecules. Low-molecular-weight bis-UPy-oligocaprolactones with cell adhesion promoting UPy-Gly-Arg-Gly-Asp-Ser (UPy-GRGDS) and the synergistic UPy-Pro-His-Ser-Arg-Asn (UPy-PHSRN) peptide sequences are synthesized and studied. The in vitro results indicate strong and specific cell binding of fibroblasts to the UPy-functionalized bioactive materials containing both UPy-peptides. An even more striking effect is seen in vivo where the formation of single giant cells at the interface between bioactive material and tissue is triggered.
生物活性聚合物支架是最终形成功能性组织的先决条件。在此,我们表明,基于四重氢键脲嘧啶酮(UPy)基团的超分子聚合物因其低温加工性、良好的降解性和生物相容性,非常适合用于制备此类生物活性材料。特别地,氢键的可逆性质允许采用模块化方法来控制体外和体内的细胞行为及活性。通过简单地将UPy功能化聚合物与UPy修饰的生物分子混合,即可获得生物活性材料。合成并研究了具有促进细胞黏附的UPy-Gly-Arg-Gly-Asp-Ser(UPy-GRGDS)和协同作用的UPy-Pro-His-Ser-Arg-Asn(UPy-PHSRN)肽序列的低分子量双UPy-低聚己内酯。体外实验结果表明,成纤维细胞与含有两种UPy肽的UPy功能化生物活性材料之间存在强烈且特异性的细胞结合。在体内观察到了更显著的效果,即在生物活性材料与组织的界面处引发了单个巨细胞的形成。