Double-crosslinked bifunctional hydrogels with encapsulated anti-cancer drug for bone tumor cell ablation and bone tissue regeneration

Abstract

Many biomaterials are made and studied to provide anticancer therapy, and many other biomaterials have been developed to assist body tissue regeneration. It has been a challenge to design and produce effective multifunctional, or bifunctional, biomaterials for clinical applications to prevent cancer recurrence and, at the same time, to promote new tissue formation after surgical removal of the tumor for millions of cancer patients. In this study, bifunctional UV and Sr²⁺ double-crosslinked alginate (ALG)/allylated gelatin (GelAGE) hydrogels incorporated with polydopamine (PDA) particles were designed and made. Furthermore, doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in PDA particles. It was aimed for the new ALG/GelAGE-PDA@DOX hydrogels to exhibit anticancer synergy and hence provide combined chemotherapy and phototherapy (PTT) for bone tumor cell ablation. In vitro experiments using MG63 osteosarcoma cells showed that ALG/GelAGE-PDA@DOX hydrogels could effectively kill tumor cells through the synergy of controlled DOX release and hyperthermia ablation. It was also aimed for the new hydrogels to facilitate bone tissue regeneration at the original bone tumor site. The results of in vitro experiments demonstrated that owing to the release of Sr²⁺, the new hydrogels could promote the proliferation of rat bone mesenchymal stem cells (rBMSCs) and also the alkaline phosphatase (ALP) activity of cells, indicating their osteogenic promotion ability. The ALG/GelAGE-PDA@DOX hydrogels have therefore exhibited great potential for the treatment of bone tumor-related defects.

Keywords: Anti-tumor effect; Bone regeneration; Drug delivery; Hydrogel; Polydopamine.