Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus

Abstract

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds

“…Regeneration of osteonecrotic bone defects using a tissue engineering approach is seen as a potential alternative to the traditional use of bone grafts, as they are available in an unlimited supply and there is no fear of disease transmission, additional donor site morbidity, immune rejection, or pathogen transfer. For these reasons, there is currently an extremely high interest in functional biomimetic biomaterials [ 5 , 6 , 36 ]. To achieve this goal, biocompatible scaffolds are developed that mimic the architecture of the extracellular matrix of the target bone as closely as possible to achieve the induction of new functional bone tissue [ 37 ].…”

“…Different treatment modalities (high tibial osteotomy, bone grafting, and core decompression) were used with different limitations, such as invasiveness, comorbidity of the autologous cancellous bone harvest site, a second surgery to remove osteosynthesis material, necrosis of autologous grafts, or lack of biomechanical stability of the alloplastic biomaterial used to fill the defect [ 4 ]. Despite the lifelong regenerative and remodeling capacity of the bone, large bone defects and those in the main loading zones of the joint require more treatment intervention [ 5 ]. Currently, orthopedic surgeons prefer a biological replacement for younger patients and a permanent and metallic surface replacement for older people [ 6 , 7 ].…”

“…In the field of bone tissue engineering, due to the presence of bone marrow stem cells and osteoblasts at the site of injury, emphasis on the osteoconductive properties of the scaffold alone has been crucial; thus, a critical goal is to build osteoinductive scaffolds that can deliver regenerative signals to cells [ 8 , 9 ]. Despite the success of autologous bone grafts in reconstructing and healing bone defects, the limited bone resources in grafts and the disadvantages of the above alternative treatment strategies motivate the design and fabrication of new biologically active biomaterials for bone regeneration [ 5 , 10 ].…”

“…This is one of the main goals of bone tissue engineering: the design and fabrication of 3D scaffolds that are not only biocompatible, biodegradable, and specifically porous, but also have a mechanical stability appropriate to bone tissue and additionally possess bioactivity [ 5 , 11 , 12 ]. Nowadays, various classes of materials are available in the field of biomaterial sciences.…”

Materials science and design principles of therapeutic materials in orthopedic and bone tissue engineering

“…Refinements in surgical procedures, implant construction and postoperative care have greatly increased patient outcomes for complex injuries and abnormalities caused by high energy trauma, cancer, developmental deformity and surgery. [101][102][103][104][105] Extensive soft tissue damage, inadequate surgical techniques, infections, and biomechanical instability can lead to large defects with limited internal regenerative potential. These defects represent a significant surgical challenge, associated with high socio-economic costs and have a high impact on the quality of life of patients.…”