Collagen binding and mimetic peptide-functionalized self-assembled peptide hydrogel enhance chondrogenic differentiation of human mesenchymal stem cells.

ABSTRACT

The avascular structure and low cell migration to the damaged area due to the low number of cells do not allow spontaneous repair of the articular cartilage tissue. Therefore, functional scaffolds obtained from biomaterials are used for the regeneration of cartilage tissue. Here, we functionalized one of the self-assembling peptide (SAP) scaffolds KLD (KLDLKLDLKLDL) with short bioactive motifs, which are the α1 chain of type II collagen binding peptide WYRGRL (C1) and the triple helical collagen mimetic peptide GFOGER (C2) by direct coupling. Our goal was to develop injectable functional SAP hydrogels with proper mechanical characteristics that would improve chondrogenesis. Scanning electron microscopy (SEM) was used to observe the integration of peptide scaffold structure at the molecular level. To assure the stability of SAPs, the rheological characteristics and degradation profile of SAP hydrogels were assessed. The biochemical study of the DNA, glycosaminoglycan (GAG), and collagen content revealed that the developed bioactive SAP hydrogels greatly increased hMSCs proliferation compared with KLD scaffolds. Moreover, the addition of bioactive peptides to KLD dramatically increased the expression levels of important chondrogenic markers such as aggrecan, SOX-9, and collagen Type II as evaluated by real-time polymerase chain reaction (PCR). We showed that hMSC proliferation and chondrogenic differentiation were encouraged by the developed SAP scaffolds. Although the chondrogenic potentials of WYRGRL and GFOGER were previously investigated, no study compares the effect of the two peptides integrated into 3-D SAP hydrogels in chondrogenic differentiation. Our findings imply that these specifically created bioactive peptide scaffolds might help enhance cartilage tissue regeneration.