RGD-conjugated crosslinked chitosan scaffolds for culture and osteogenic differentiation of mesenchymal stem cells

Chitosan has been a popular material for fabrication of tissue engineering scaffolds and has been reported to be a suitable substrate for the culture and differentiation of mesenchymal stem cells (MSCs). In this study, chitosan scaffolds were conjugated with RGD peptides to further enhance the functions of chitosan scaffolds. Biomimetic chitosan scaffolds were prepared using two types of chitosan derivatives, one containing photoreactive azides for UV-crosslinking and the other tethered with RGD peptides. We first fabricated several different chitosan scaffolds with various azide contents to evaluate the mechanical properties of the chitosan scaffolds. The attachment and proliferation of MSCs were greatly enhanced in RGD-incorporated chitosan scaffolds compared with the control scaffolds without RGD conjugation during 2 weeks of culture without osteoinduction. RGD-conjugation also significantly enhanced mineralization of MSCs after 14 days of osteogenic culture. Taken together, the results indicate that the conjugation of RGD peptides to chitosan scaffolds allows for a more favorable microenvironment for MSCs to grow, differentiate into osteoblasts and produce mineralized matrix compared with unmodified chitosan scaffolds. These findings demonstrate the potential of RGD-incorporated, crosslinked chitosan scaffolds for bone tissue engineering applications.

► We synthesized RGD and azide-conjugated chitosan for fabrication of chitosan scaffolds.
► The mechanical strength of chitosan scaffolds was increased with azide contents.
► RGD-conjugation enhanced the adhesion and growth of MSCs in chitosan scaffolds.
► RGD-conjugation enhanced the mineralization of MSCs in chitosan scaffolds.
► RGD-conjugation strengthened MSC/scaffold constructs after osteogenic culture.