Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation

Abstract

Photocrosslinked, biodegradable hydrogels have been extensively investigated for biomedical applications, including drug delivery and tissue engineering. Here, dextran (DEX) was chemically modified with mono(2-acryloyloxyethyl)succinate (MAES) via an esterification reaction, resulting in macromers that could be photocrosslinked to form hydrolytically degradable hydrogels. Hydrogel swelling ratio and degradation rate were controlled by varying the degree of MAES modification. Thiolated cell adhesion peptides (GRGDSPC) were conjugated to acrylated dextran via thiol–acrylate reaction to regulate the interactions of human mesenchymal stem cells (hMSCs) with the photocrosslinkable hydrogels. The hydrogels permitted sustained release of short interfering RNA (siRNA) over 7 weeks and were cytocompatible with hMSCs. Sustained presentation of siRNA from these photocrosslinked DEX hydrogels enhanced the osteogenic differentiation of encapsulated hMSCs. These DEX hydrogels with tunable siRNA delivery and cell adhesive properties may provide an excellent platform for bioactive molecule delivery and tissue regeneration applications.