PRINT-CHEMO · To develop 3D bioPRINTed osteoinductive constructs that deliver CHEMOtherapeutics within large bone defects that are surgically created when removing bone tumours.

Osteosarcoma is the most commonly diagnosed bone tumour with most of these cases being in children and adolescents. Each year over 4,000 new cases of osteosarcoma are diagnosed in the United States. Osteosarcoma predominantly initiates in the metaphysis of long bones, such as the distal femur, proximal tibia and proximal humerus. Over 50% of these tumours are relatively resistant to radiation therapy, due to the molecular aberration of the tumour. The current gold standard for treatment is tumour resection and adjuvant chemotherapy, with a 5-year survival rate of 61.6% in patients aged 0-24 years old. Approximately one-third of patients diagnosed with osteosarcoma are expected to have a relapse, with only 15% of these patients surviving the disease a second time. Therefore, due to the young age of initial diagnosis, the management of this disease is a challenging and costly exercise, which has a significant socioeconomic cost, estimated to be €14.7 billion in Europe and $45 billion in the USA in the last 18 years. While significant progress has been made in trying to understand the intra-tumour heterogeneity and the evolutionary pattern of a subset of clones within the tumour, thus far, no major changes in treatment and outcome have been achieved. The hypothesis of PRINT-CHEMO is that localised delivery of self-assembled dendritic nanoparticles used as a first wave of treatment to deliver miR-194, a tumour suppressive gene, to the cells along with the delivery of nanoparticles loaded with chemotherapeutics would lead to higher survival rates and less side effects than systemic delivery of a higher dose of drug. Furthermore, PRINT-CHEMO not only aims to treat the diseased tissue but using 3D printing provide the necessary cues to allow for the body to regenerate the damaged bone caused due to tumour resection.