Supramolecular GAG-like Self-Assembled Glycopeptide Nanofibers Induce Chondrogenesis and Cartilage Regeneration

Biomacromolecules. 2016 Feb 8;17(2):679-89. doi: 10.1021/acs.biomac.5b01669. Epub 2016 Jan 13.


Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / physiology*
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chondrogenesis
  • Glycopeptides / chemistry*
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / chemistry
  • Male
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Molecular Mimicry
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Rabbits
  • Regeneration*
  • Scattering, Small Angle
  • Tissue Scaffolds / chemistry
  • X-Ray Diffraction


  • Cd44 protein, mouse
  • Glycopeptides
  • Hyaluronan Receptors
  • Hyaluronic Acid