Biomimetic Nanofibrillar Hydrogel with Cell-Adaptable Network for Enhancing Cellular Mechanotransduction, Metabolic Energetics, and Bone Regeneration

• Published in: Journal of the American Chemical Society 2023-07, Vol.145 (28), p.15218-15229
• Main Authors: Xie, Xian, Li, Zhuo, Yang, Xuefeng, Yang, Boguang, Zong, Zhixian, Wang, Xuemei, Duan, Liting, Lin, Sien, Li, Gang, Bian, Liming
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.3c02210

The natural extracellular matrix, with its heterogeneous structure, provides a stable and dynamic biophysical framework and biochemical signals to guide cellular behaviors. It is challenging but highly desirable to develop a synthetic matrix that emulates the heterogeneous fibrous structure with macroscopic stability and microscopical dynamics and contains inductive biochemical signals. Herein, we introduce a peptide fiber-reinforced hydrogel in which the stiff ß-sheet fiber functions as a multivalent cross-linker to enhance the hydrogel’s macroscopic stability. The dynamic imine cross-link between the peptide fiber and polymer network endows the hydrogel with a microscopically dynamic network. The obtained fibrillar nanocomposite hydrogel, with its cell-adaptable dynamic network, enhances cell–matrix and cell–cell interactions and therefore significantly promotes the mechanotransduction, metabolic energetics, and osteogenesis of encapsulated stem cells. Furthermore, the hydrogel can codeliver a fiber-attached inductive drug to further enhance osteogenesis and bone regeneration. We believe that our work provides valuable guidance for the design of cell-adaptive and bioactive biomaterials for therapeutic applications.