Probiotic Biofilm Modified 3D-Printing Scaffolds for Improving Chemo-Immunotherapy of Bone Tumor and Promoting Osteogenesis

Tumor recurrence and unfavorable bacterial biofilm formation on implants after bone tumor resection remain challenging in clinical settings. However, this dilemma also provides inspiration for the development of bioactive implants and a new route for the management of bone tumors through biofilm formation. Here, based on the characteristic that bacteria prefer to adhere to implants, 3D-printing bioceramic scaffolds modified with probiotic biofilms are designed to augment antitumor immunity. In comparison with Akkermansia muciniphila, Lactobacillus rhamnosus GG (LGG) is demonstrated to more easily form biofilms on bioceramics and is selected to engineer etched bioceramics. The LGG biofilm subjected to pasteurization guarantees good biocompatibility and enhanced doxorubicin (Dox) loading. Furthermore, the LGG biofilm combined with Dox imparts the scaffolds with multiple properties of direct chemo-killing for tumor cells and potent immune activation. The modified scaffolds efficiently inhibit bone tumor recurrence and bone metastasis in murine tumor model receives surgical resection. Moreover, based on 3D-printing technology, the probiotic biofilm modified scaffolds with adjustable shapes are also demonstrated to repair shape-specific bone defects after tumor elimination. Collectively, the multifunctional 3D-printing scaffolds realize the integrated treatment of tumor elimination and bone repair, providing a promising strategy for clinical treatment of bone tumors. Probiotic biofilm modified 3D-printing scaffolds are developed for management of bone tumors and osteogenesis. Remarkable curative effects and systematic immune protection from chemo-immunotherapy mediated by probiotic biofilm modified scaffolds are demonstrated. The multifunctional 3D-printing scaffolds realize the integrated treatment of tumor elimination and bone repair, providing a promising strategy for clinical treatment of bone tumors.image