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

  • J Am Chem Soc. 2023 Jul 19;145(28):15218-15229. doi: 10.1021/jacs.3c02210.
Xian Xie  1 ,  Zhuo Li  1 ,  Xuefeng Yang  2 ,  Boguang Yang  3 ,  Zhixian Zong  3 ,  Xuemei Wang  1 ,  Liting Duan  1 ,  Sien Lin  3 ,  Gang Li  3 ,  Liming Bian  4  5  6  7
Affiliations
  • 1. Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong 999077, P. R. China.
  • 2. Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, P. R. China.
  • 3. Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, P. R. China.
  • 4. School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P. R. China.
  • 5. Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, P. R. China.
  • 6. Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, P. R. China.
  • 7. National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
PMID: 37428960 DOI: 10.1021/jacs.3c02210
Abstract

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.

Products