Scaffold 3D-printed From Metallic Nanoink Simultaneously Eradicates Tumor And Repairs Tumor-associated Bone Defects

Despite great efforts to treat cancer,it remains one of the difficult problems facing the medical community today.For a large number of solid tumors,including the most common breast cancer in women,distant metastasis has become one of the main causes of high mortality.One of the most common sites of metastases for breast cancer is the bone,leading to the formation of bone-metastatic tumor.The current treatments for bone-metastatic tumor mainly involve surgery,chemotherapy and radiotherapy.Surgery,as the most commonly clinical treatment for bone metastases,will cause large bone defects that are difficult to self-heal during the removal process.Moreover,surgery cannot completely remove cancer cells,which may easily lead to tumor recurrence and has certain limitations.Chemotherapy is a systemic treatment,which is highly toxic to the whole body.Meanwhile,the use of chemotherapy drugs could reduce the ability of bone tissue self-healing.Although radiotherapy could alleviate bone pain and other problems caused by bone metastases to a certain extent,it is easy to cause bone marrow suppression.Therefore,the design and preparation of novel biomaterials that could be used to kill possible residual tumor cells while promoting postoperative bone defect repair is of great clinical significance.Based on two stages of bone metastases treatment and bone defect repair during the treatment of bone metastases,a bifunctional 3D printed scaffold embedded with metallic PDA nanoparticles containing Fe3+and Mg2+(FeMg-NPs)were fabricated for tumor-related bone defect repair.The details are as follows:In this paper,bimetallic PDA nanoparticles(FeMg-NPs)containing Fe3+ and Mg2+ were firstly synthesized under alkaline conditions.The above nanoparticles were mixed with the homogeneous composite solution of β-tricalcium phosphate/poly(lactic-co-glycolic acid)/dichloromethane(TCP/PLAG/DCM)and then was 3D-printed layer-by-layer using a V-shape nozzle syringe to form FeMg-NPs/TCP/PLGA scaffolds(FeMg-SC).Implantation of FeMg-SC at the surgical resection site of bone metastases could effectively and continuously release metal ions Fe3+ and Mg2+in the process of slow degradation.Fe3+ exerted a chemodynamic therapy to synergize with the photothermal therapy induced by PDA under NIR laser,which efficiently eliminated the bone-metastatic tumor.Meanwhile,sustained release of osteoinductive Mg2+ in the bone defect promoted the formation of new bone.Therefore,in situ implantation of FeMg-SC after bone-metastatic tumor surgery is expected to eliminate the tumor cells that have not been removed during surgery and avoid tumor recurrence.Meanwhile,the scaffold continued to promote the formation of new bone during the process of degradation,providing a new therapeutic strategy for the ablation of residual tumor cells and the repair of bone defects after bone-metastatic tumor surgery.