Assembly of Recombinant Proteins into β-Sheet Fibrillating Peptide-Driven Supramolecular Hydrogels for Enhanced Diabetic Wound Healing

作者：Zhao Guo, Xing Liu, Yan Xia, Jie Wang, Jiaqi Li, Liping Wang, Yimiao Li, Shuang Jia, Yinan Sun, Jian Q. Feng, Jingxia Huang, Yuxin Dong, Liyao Wang, Xinyu Li · 发表于：ACS Biomaterials Science & Engineering · 年份：2024 · DOI：10.1021/acsbiomaterials.4c01723 · 被引用次数：3 · 研究领域：Collagen: Extraction and Characterization、Supramolecular Self-Assembly in Materials、Bone and Dental Protein Studies

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 o...