Guo Zhao, Liu Xing, Xia Yan, Wang Jie, Li Jiaqi, Wang Liping, Li Yimiao, Jia Shuang, Sun Yinan, Feng Jian, Huang Jingxia, Dong Yuxin, Wang Liyao, Li Xinyu
Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, School of Life Sciences, Inner Mongolia University, Hohhot 010020, PR China.
ACS Biomater Sci Eng. 2025 Jan 13;11(1):228-238. doi: 10.1021/acsbiomaterials.4c01723. Epub 2024 Dec 9.
Supramolecular hydrogels offer a noncovalent binding platform that preserves the bioactivity of structural molecules while enhancing their stability, particularly in the context of diabetic wound repair. In this study, we developed protein-peptide-based supramolecular hydrogels by assembling β-sheet fibrillizing peptides (designated Q11) with β-tail fused recombinant proteins. The Q11 peptides have the ability to drive the gradated assembly of N- or C-terminal β-sheet structure (β-tail) fused recombinant proteins. We first investigated the assembly properties of Q11 and assessed its stability under varying pH and temperature conditions by combining Q11 with two β-tail fused fluorescent proteins. The results showed that Q11 enhanced the tolerance of the fluorescent proteins to changes in pH and temperature. Building upon these findings, we designed collagen-like proteins and Sonic Hedgehog-fused recombinant proteins (CLP-Shh) that could be assembled with Q11 to form peptide-protein supramolecular hydrogels. These hydrogels demonstrated the ability to improve cell viability and migration and upregulate key markers of cell growth. Further in vivo studies revealed that the Q11-driven supramolecular hydrogel effectively enhances diabetic wound healing and epidermal regeneration by promoting the expression of epidermal-related proteins and immune factors. This study highlights the potential of supramolecular hydrogels for clinical applications and their promise in the development of biofunctional hydrogels for therapeutic use.
超分子水凝胶提供了一个非共价结合平台，该平台在增强结构分子稳定性的同时保留其生物活性，尤其在糖尿病伤口修复的背景下。在本研究中，我们通过将β-折叠纤维化肽（命名为Q11）与β-尾融合重组蛋白组装，开发了基于蛋白质-肽的超分子水凝胶。Q11肽能够驱动N端或C端β-折叠结构（β-尾）融合重组蛋白的分级组装。我们首先研究了Q11的组装特性，并通过将Q11与两种β-尾融合荧光蛋白结合，评估了其在不同pH和温度条件下的稳定性。结果表明，Q11增强了荧光蛋白对pH和温度变化的耐受性。基于这些发现，我们设计了可以与Q11组装形成肽-蛋白质超分子水凝胶的类胶原蛋白和音猬因子融合重组蛋白（CLP-Shh）。这些水凝胶表现出改善细胞活力和迁移以及上调细胞生长关键标志物的能力。进一步的体内研究表明，Q11驱动的超分子水凝胶通过促进表皮相关蛋白和免疫因子的表达，有效地促进糖尿病伤口愈合和表皮再生。本研究突出了超分子水凝胶在临床应用中的潜力及其在开发用于治疗用途的生物功能水凝胶方面的前景。
