Mechanobiologically-optimized non-resorbable artificial bone – a new paradigm in patient-matched scaffold-guided bone regeneration

Patient-matched scaffold guided bone regeneration (SGBR) has been poised to revolutionize the management of critical-sized bone defects due to trauma, tumors, infection, and congenital deformities. However, translation has been hampered by the focus on bioresorbable scaffolds where the rate of scaffold degradation needs to be precisely and predictably matched to the rate of new bone formation. Furthermore, resorbable ceramics and polymers require augmentation by metal plates to overcome their mechanical limitations under load. Consequently, there are no published studies using SGBR for segmental defects without metal plates, which cause stress shielding and X-ray perturbation. Even with augmentation, very few studies use animal models where the loads are comparable to humans. Segmental defects of the mandible represent one of the most challenging examples of critical-sized bone defects due to the high tensile and shear stresses encountered during mastication. The ovine mandible is an excellent model because the high and repetitive loads exceed those encountered in humans. Here, we describe the first successful long-term reconstruction of ovine segmental mandibulectomy defects using permanent, patient-matched, numerically optimized, 3D-printed, thermally toughened, plasma-treated, and selectively-laser-sintered polyetherketone gyroid scaffolds. The scaffolds house a resorbable ceramic lattice infused with a stem cell laden hydrogel and serve as an osteoinductive reservoir of calcium. Durable clinical performance and osseointegration was established in vivo and ex vivo, indicating for the first time that there is a reliable and translatable patient-matched SGBR alternative to traditional bone grafts and metal plate fixation.