Nanoporous 3D-printed scaffolds for local doxorubicin delivery in bone metastases secondary to prostate cancer

The spine is the most common site of bone metastasis, often originating from prostate, lung, and breast cancers. High systemic doses of chemotherapeutics such as doxorubicin (DOX), cisplatin, or paclitaxel often have severe side effects. Surgical removal of spine metastases also leaves large defects which cannot spontaneously heal and require bone grafting. To circumvent these issues, we designed an approach for local chemotherapeutic delivery within 3D-printed scaffolds which could also potentially serve as a bone substitute. Direct treatment of prostate cancer cell line LAPC4 and patient derived spine metastases cells with 0.01 μM DOX significantly reduced metabolic activity, proliferation, migration, and spheroid growth. We then assessed uptake and release of DOX in a series of porous 3D-printed scaffolds on LAPC4 cells as well as patient-derived spine metastases cells. Over seven days, 60-75% of DOX loaded onto scaffolds could be released, which significantly reduced metabolic activity and proliferation of both LAPC4 and patient derived cells, while unloaded scaffolds had no effect. Porous 3D-printed scaffolds may provide a novel and inexpensive approach to locally deliver chemotherapeutics in a patient-specific manner at tumor resection sites. With a composite design to enhance strength and promote sustained drug release, the scaffolds could reduce systemic negative effects, enhance bone repair, and improve patient outcomes.