3D printed titanium cages combined with the Masquelet technique for the reconstruction of segmental femoral defects: Preliminary clinical results and molecular analysis of the biological activity of human-induced membranes

INTRODUCTION: Traumatic femoral segmental bone loss is a complex clinical problem, one that often requires extreme solutions. This study examines a new treatment strategy for segmental bone loss using patient-specific 3D printed titanium cages in conjunction with the Masquelet technique. METHODS: The study was composed of a clinical observational case series, and a basic science investigation to evaluate the biological activity of the induced membranes using histology, immunohistochemistry (IHC), and gene expression analysis. Eligible patients were: adult; post-traumatic; with segmental femoral defects; minimum follow-up 1 year; managed under a 2-stage protocol, with an interim antibiotic poly (methyl methacrylate) (PMMA) spacer. Definitive reconstruction was completed with exchange to a 3D printed custom titanium cage filled with bone graft, and stabilized with either an intramedullary (IM) nail or a lateral locked plate. RESULTS: Patient-specific 3D printed titanium cages were used in 5 consecutive patients to reconstruct post-traumatic segmental femoral defects. The mean interval between stages was 100.2 days (83–119 days), the mean defect length was 14.0 cm (10.3–18.4 cm), and the mean bone defect volume measured 192.4 cc (114–292 cc). The mean length of follow-up was 21.8 months (12–33 months). There were no deep infections, fractures, nerve injuries, loss of alignment, or nonunions identified during the period of follow-up. All of the patients achieved union clinically and radiographically. Histology and IHC demonstrated a greater number of vessels, cell nuclei, and extensive staining for cluster of differentiation 68 (CD68), platelet and endothelial cell adhesion molecule 1 (PECAM-1), and vascular endothelial growth factor (VEGF) in the induced membranes compared to local fascia controls. Gene expression analysis revealed significant differential regulation of essential genes involved in inflammatory, angiogenic, and osteogenic pathways [interleukin 6 (IL-6), nuclear factor kappa B1 (NF-κB1), receptor activator of nuclear factor kappa-β ligand (RANKL), vascular endothelial growth factor A (VEGFA), angiogenin (ANG), transforming growth factor, beta 1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), growth differentiation factor 5 (GDF-5), growth differentiation factor 10 (GDF-10), and runt-related transcription factor 2 (RUNX-2)] in the induced membranes. CONCLUSIONS: This study demonstrates that the use of a patient-specific 3D printed custom titanium cage, inserted into an induced membrane in a 2-stage protocol, can achieve very acceptable clinical outcomes in selected cases of post-traumatic femoral segmental defects. Patient-specific 3D printed titanium cages, used in conjunction with the Masquelet technique, are a promising new treatment option for managing complex trauma patients with femoral bone loss. LEVEL OF EVIDENCE: Level IV (observational case series).