Tetsworth Kevin, Woloszyk Anna, Glatt Vaida
Royal Brisbane and Women's Hospital, Herston, Queensland.
Orthopaedic Research Centre of Australia, Brisbane, Queensland, Australia.
OTA Int. 2019 Mar 12;2(1):e016. doi: 10.1097/OI9.0000000000000016. eCollection 2019 Mar.
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.
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.
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.
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 IV (observational case series).
创伤性股骨节段性骨缺损是一个复杂的临床问题，通常需要采取极端的解决方法。本研究探讨了一种使用患者特异性3D打印钛笼结合Masquelet技术治疗节段性骨缺损的新策略。
本研究包括一个临床观察病例系列和一项基础科学研究，通过组织学、免疫组织化学（IHC）和基因表达分析来评估诱导膜的生物活性。符合条件的患者为：成年人；创伤后；股骨节段性缺损；最短随访1年；采用两阶段方案治疗，中间使用抗生素聚甲基丙烯酸甲酯（PMMA）间隔物。最终重建通过更换为填充骨移植材料的3D打印定制钛笼完成，并用髓内（IM）钉或外侧锁定钢板固定。
连续5例患者使用患者特异性3D打印钛笼重建创伤后股骨节段性缺损。两阶段之间的平均间隔为100.2天（83 - 119天），平均缺损长度为14.0厘米（10.3 - 18.4厘米），平均骨缺损体积为192.4立方厘米（114 - 292立方厘米）。平均随访时间为21.8个月（12 - 33个月）。随访期间未发现深部感染、骨折、神经损伤、对线不良或骨不连。所有患者在临床和影像学上均实现了骨愈合。组织学和IHC显示，与局部筋膜对照相比，诱导膜中有更多的血管、细胞核，并且分化簇68（CD68）、血小板和内皮细胞黏附分子1（PECAM - 1）以及血管内皮生长因子（VEGF）的染色广泛。基因表达分析显示，诱导膜中参与炎症、血管生成和成骨途径的关键基因[白细胞介素6（IL - 6）、核因子κB1（NF - κB1）、核因子κB受体活化因子配体（RANKL）、血管内皮生长因子A（VEGFA）、血管生成素（ANG）、转化生长因子β1（TGF - β1）、骨形态发生蛋白 - 2（BMP - 2）、生长分化因子5（GDF - 5）、生长分化因子10（GDF - 10）和 runt相关转录因子2（RUNX - 2）]存在显著的差异调节。
本研究表明，在两阶段方案中将患者特异性3D打印定制钛笼插入诱导膜中，在创伤后股骨节段性缺损的特定病例中可取得非常理想的临床效果。患者特异性3D打印钛笼与Masquelet技术联合使用，是治疗伴有股骨骨缺损的复杂创伤患者的一种有前景的新治疗选择。
IV级（观察性病例系列）。
