Nanoengineered Injectable Hydrogels for On-Demand and Localized Therapeutic Delivery

Abstract

“Smart” hydrogels are an emerging class of biomaterials that respond to multiple external stimuli and investigated for a range of biomedical applications, including therapeutic delivery, and regenerative engineering. Stimuli-responsive nanogels based on thermoresponsive polymers such as poly (N-isopropyl acrylamide) (PNIPAM) and magnetic nanoparticles (MNPs), are developed as “smart carriers” for on-demand delivery of therapeutic biomolecules via magneto-thermal activation. However due to their small size and systemic introduction, these PNIPAM/MNPs nanogels result in limited control over long-term, localized therapeutic delivery. Here, we developed an injectable nanoengineered hydrogel loaded with PNIPAM/MNPs for localize on-demand delivery of therapeutics (doxorubicin (DOX)). We have engineered shear-thinning and self-recoverable hydrogels by modulating crosslinking density of our methacrylated gelatin (GelMA) network. PNIPAM/MNPs nano-gels loaded with DOX were entrapped within the GelMA pre-polymer solution prior to crosslinking. The temperature and magnetic field dependent release of loaded DOX was observed from the nano-engineered hydrogels (GelMA/(PNIPAM/MNPs)). The in vitro efficacy of DOX released from injectable nanoengineered hydrogels was investigated using preosteoblast and osteosarcoma cells. Overall, these results demonstrated that the injectable nanoengineered hydrogels can be used for on-demand and localized therapeutic delivery for biomedical applications

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