Towards Transforming the Current Clinical Approach to Bone Tumours With Innovative Customized 3d-Printed Bioresorbable Implants

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, yet survival rates have stagnated for over four decades. Current treatment involves tumor resection combined with neoadjuvant and adjuvant chemotherapy, but this approach faces significant challenges. Up to 50% of patients with localized disease experience recurrence, often at the primary site, and disease relapse drastically reduces survival rates. Additionally, chemotherapy causes severe systemic toxicities, impacting quality of life. Limb-salvage surgery (LSS) is performed in 85–90% of OS patients to avoid amputation. However, LSS is associated with high complication rates: 30–40% of endoprosthetics fail due to growth-related loosening or infection, and ~23% of bone grafts fail due to rejection or incomplete healing. Addressing these limitations requires innovative solutions that simultaneously control tumor recurrence and restore bone integrity. To address these challenges, we developed 3D-printed bioresorbable scaffolds with a Voronoi-tessellated design for two complementary concepts: localized chemotherapy delivery and scaffold-guided bone regeneration (SGBR). In an orthotopic OS rat model, lactoprene/β-TCP (60/40%) scaffolds combined with doxorubicin (DOX)-loaded gelatin methacryloyl (GelMA) hydrogels provided localized drug delivery after tumor resection. This approach significantly inhibited tumour regrowth for up to six weeks and reduced systemic toxicity compared to intravenous chemotherapy. Interestingly, local DOX also appeared to prevent the development of lung metastases compared to untreated and systemic chemotherapy groups. In a separate study, the same scaffold design, combined with recombinant human bone morphogenetic protein-2 (rhBMP-2), was evaluated for its ability to regenerate bone in a critical-sized defect model. Micro-CT imaging demonstrated that the combination of scaffold and rhBMP-2 could support critical sized defect healing within 16 weeks. Histological analyses revealed robust cortical and trabecular bone formation, with extensive integration into the scaffold's porous architecture, demonstrating the feasibility of this combination in SGBR. Future studies will investigate the convergence of localized chemotherapy and SGBR into a single-step surgical intervention. Combining DOX-loaded hydrogels with rhBMP-2-enhanced scaffolds aims to simultaneously prevent OS recurrence and regenerate bone after tumor resection. This dual-function strategy represents a significant advancement in orthopaedic oncology, with the potential to improve outcomes and quality of life for OS patients by addressing both tumor control and bone regeneration in a single surgical procedure.