Cytocompatible Catalyst-Free Photodegradable Hydrogels for Light-Mediated RNA Release To Induce hMSC Osteogenesis

Macroscopic hydrogels provide valuable platforms for controlling the release of genetic materials such as small interfering RNA (siRNA) and microRNA (miRNA) for biomedical applications. However, after these hydrogels are formed, it is challenging to alter the release rate of genetic materials. In this report, a Michael addition catalyst-free photodegradable poly(ethylene glycol) (PEG)-based hydrogel system has been developed that provides an active means of controlling the release of genetic materials postgelation using external UV light application. Photodegradation of photolabile linkages in the hydrogel network changes the hydrogel physiochemical properties such as swelling and degradation rate, augmenting the release rate of loaded genetic materials. In the absence of UV light, RNAs were released in a sustained fashion from both photodegradable and nonphotodegradable hydrogels. In contrast, RNA release rate from the photodegradable hydrogels was accelerated via UV light application, whereas it was not elevated with nonphotodegradable hydrogels. Regardless of the UV light exposure to the hydrogels, released siRNA against green fluorescent protein (siGFP) retained its bioactivity via effectively silencing GFP expression in destabilized GFP (deGFP)-expressing HeLa cells cultured in monolayer. Moreover, cells encapsulated in these hydrogels exhibited high cell viability, and loaded siGFP inhibited GFP expression of encapsulated deGFP-expressing HeLa cells with or without UV light application to the hydrogels. Importantly, released siRNA targeting noggin (siNoggin) and miRNA-20a from the hydrogels, with and without UV light application, induced osteogenic differentiation of human mesenchymal stem cells (hMSCs). This photodegradable hydrogel system may be a promising strategy for real-time, user-controlled release of genetic materials for tissue engineering and treatment of diseases such as cancer.