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

Abstract

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.

Adipose-Derived Stem Cells Cocultured with Chondrocytes Promote the Proliferation of Chondrocytes

“…The results confirmed that ADSCs and TGF- β 1 can inhibit the expression of these two proteins to a certain extent, which can also indicate that ADSCs play a role in promoting the regeneration of cartilage. In the present study, we confirmed that ADSCs can promote the release of GAG, and SOX9, PGC-1 α , and a series of cartilage regeneration marker proteins [29–32] expression in chondrocytes can be promoted by coculture with ADSCs. This further showed that ADSCs can not only promote the proliferation of cartilage cells, but also have a protective effect on the regeneration of cartilage cells and this effect is similar to that of TGF- β 1.…”

Self‐Healing Supramolecular Hydrogels for Tissue Engineering Applications

“…This gel is nontoxic in various cell lines, an important step toward utilization in vivo. Additionally, both in vitro and in vivo differentiation of mesenchymal stem cells into chondrocytes without the use of exogenous growth factors was reported in hyaluronate and heparin mimicking PA hydrogels …”

Peptide-Based Materials for Cartilage Tissue Regeneration

“…It was also shown in the study of Yaylaci et al hyaluronic acid mimetic self-assembled peptide nanofiber gels enhance the chondrogenesis of MSCs and cartilage regeneration (Fig. 7.3) (Ustun Yaylaci et al 2016). As such, selfassembled peptide gels have recently emerged as a class of next-generation biomaterials for tissue engineering applications.…”