Thesis presented December 08, 2022

Abstract:
Critical-size bone defects are unable to heal by themselves during the patient’s lifetime. Autologous bone graft, the current gold standard to treat these defects, is associated with several drawbacks. Scaffolds are being developed as an alternative to autologous bone graft. However, scaffolds alone are not sufficient to repair impaired bone defects and require modifications such as the addition of the osteoinductive biomolecule bone morphogenetic protein 2 (BMP-2). Biomimetic polyelectrolyte films made of hyaluronic acid and poly(L-lysine) have been engineered to serve as a reservoir for BMP-2 and release it in a controlled manner in time and space. The objectives of this PhD thesis were to prove that it is possible to repair critical-size bone defects in large animals by combining a 3D-printed architectured scaffold with a 2D osteoinductive surface coating, and to study the influence of scaffold internal geometry on bone regeneration in order to optimize it. To this end, 3D-printed polymeric scaffolds made by fused deposition modeling, coated with a biomimetic film, and loaded with BMP-2 were developed to repair two types of critical-size bone defects: a mandibular bone defect in minipigs and a metatarsal bone defect in sheep. The in vitro and in vivo biocompatibility of these bioactive scaffolds were proved according to ISO standards. The dose of BMP-2 was shown to influence bone regeneration. Furthermore, we showed that scaffold internal geometry, notably pore shape, influenced bone regeneration. The bioactive scaffolds developed contained low BMP-2 doses compared to the commercially available products. This work opens perspectives for the personalized treatment of large bone defects in the clinic.

Keywords:
Medical device, bone tissue engineering, bioactivity, 3D printing