3D-printed Mg-substituted hydroxyapatite/gelatin methacryloyl hydrogels encapsulated with PDA@DOX particles for bone tumor therapy and bone tissue regeneration

Abstract

The development of bifunctional scaffolds for clinical applications, aimed at preventing tumor recurrence and promoting bone tissue regeneration simultaneously at the surgical site, is imperative in repairing bone tumor-related defects. In the current study, Mg-substituted hydroxyapatite (MgHAp) nanocomposites were synthesized via a biomineralization process. Doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in polydopamine (PDA) particles to synthesize PDA@DOX particles. MgHAp/gelatin methacryloyl (GelMA) hydrogels encapsulated with PDA@DOX particles were designed and fabricated to construct MgHAp/GelMA-PDA@DOX hydrogels via 3D printing. The 3D-printed MgHAp/GelMA-PDA@DOX hydrogels exhibited antitumor synergy by providing combined chemotherapy and phototherapy for bone tumor cell ablation. The hydrogels showed a good photothermal effect and could induce hyperthermia upon irradiation with an 808 nm near-infrared (NIR) laser. Moreover, MgHAp/GelMA-PDA@DOX hydrogels could release DOX sustainably and controllably. In vitro experiments demonstrated that 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could effectively eradicate MG63 cells through the synergy of induced hyperthermia and DOX release. Furthermore, due to the sustained release of Mg2+, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could promote the proliferation of rat bone marrow-derived mesenchymal stem cells and facilitate alkaline phosphatase activity and the expression of osteogenic genes, such as osteocalcin (Ocn), type I collagen (Col1), runt-related transcription factor-2 (Runx2), and bone morphogenetic protein-2 (Bmp2), indicating their excellent osteogenic effect. As a result, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels showed great potential in the treatment of bone tumor-related defects by effectively killing tumor cells and simultaneously promoting bone tissue regeneration.