Department of Chemistry, Bogazici University, Istanbul 34342, Turkey.
Center for Life Sciences and Technologies, Bogazici University, Istanbul 34342, Turkey.
Bioconjug Chem. 2022 May 18;33(5):839-847. doi: 10.1021/acs.bioconjchem.2c00094. Epub 2022 Apr 21.
In recent years, stimuli-responsive degradation has emerged as a desirable design criterion for functional hydrogels to tune the release of encapsulated payload as well as ensure degradation of the gel upon completion of its function. Herein, redox-responsive hydrogels with a well-defined network structure were obtained using a highly efficient thiol-disulfide exchange reaction. In particular, gelation occurred upon combining thiol-terminated tetra-arm polyethylene glycol (PEG) polymers with linear telechelic PEG-based polymers containing pyridyl disulfide units at their chain ends. Rapid gelation proceeds with good conversions (>85%) to yield macroporous hydrogels possessing high water uptake. Furthermore, due to the presence of the disulfide linkages, the thus-obtained hydrogels can self-heal. The obtained hydrogels undergo complete degradation when exposed to environments rich in thiol-containing agents such as dithiothreitol (DTT) and L-glutathione (GSH). Also, the release profile of encapsulated protein, namely, bovine serum albumin, can be tuned by varying the molecular weight of the polymeric precursors. Additionally, it was demonstrated that complete dissolution of the hydrogel to rapidly release the encapsulated protein occurs upon treating these hydrogels with DTT. Cytotoxicity evaluation of the hydrogels and their degradation products indicated the benign nature of these hydrogels. Additionally, the cytocompatible nature of these materials was also evident from a live/dead cell viability assay. One can envision that the facile fabrication and their ability to degrade on-demand and release their payload will make these benign polymeric scaffolds attractive for various biomedical applications.
近年来，刺激响应降解已成为功能水凝胶的理想设计标准，可调节包封的有效载荷的释放，并确保凝胶在完成其功能后降解。在此，使用高效的巯基-二硫交换反应获得了具有明确定义的网络结构的氧化还原响应水凝胶。特别是，当将末端巯基的四臂聚乙二醇（PEG）聚合物与线性端基含吡啶二硫基单元的线性端基 PEG 基聚合物结合时，凝胶化发生。快速凝胶化进行得很好，转化率> 85%，得到具有高吸水率的大孔水凝胶。此外，由于存在二硫键，因此获得的水凝胶可以自修复。当将所得水凝胶暴露于富含含巯基试剂（例如二硫苏糖醇（DTT）和 L-谷胱甘肽（GSH）的环境中时，它们会完全降解。此外，可以通过改变聚合物前体的分子量来调节包封的蛋白质（即牛血清白蛋白）的释放曲线。此外，通过用 DTT 处理这些水凝胶，可以证明水凝胶的快速溶解以迅速释放包封的蛋白质。水凝胶及其降解产物的细胞毒性评估表明了这些水凝胶的良性性质。此外，从活/死细胞活力测定中也可以明显看出这些材料的细胞相容性。人们可以设想，这些易于制造的材料能够按需降解并释放其有效载荷，这将使这些良性的聚合物支架在各种生物医学应用中具有吸引力。
