Three-dimensional (3D) titanium-mesh scaffolds offer many advantages over autologous bone grafting for the regeneration of challenging large segmental bone defects. Our study supports the hypothesis that endogenous bone defect regeneration can be promoted by mechanobiologically optimized Ti-mesh scaffolds. Using finite element techniques, two mechanically distinct Ti-mesh scaffolds were designed in a honeycomb-like configuration to minimize stress shielding while ensuring resistance against mechanical failure. Scaffold stiffness was altered through small changes in the strut diameter only. Honeycombs were aligned to form three differently oriented channels (axial, perpendicular, and tilted) to guide the bone regeneration process. The soft scaffold (0.84 GPa stiffness) and a 3.5-fold stiffer scaffold (2.88 GPa) were tested in a critical size bone defect model in vivo in sheep. To verify that local scaffold stiffness could enhance healing, defects were stabilized with either a common locking compression plate that allowed dynamic loading of the 4-cm defect or a rigid custom-made plate that mechanically shielded the defect. Lower stress shielding led to earlier defect bridging, increased endochondral bone formation, and advanced bony regeneration of the critical size defect. This study demonstrates that mechanobiological optimization of 3D additive manufactured Ti-mesh scaffolds can enhance bone regeneration in a translational large animal study.

三维（3D）钛网支架比自体骨移植具有许多优势，可再生具有挑战性的大型节段性骨缺损。我们的研究支持以下假设，即通过机械生物学优化的Ti-Mesh支架可以促进内源性骨缺损的再生。使用有限元技术，以蜂窝状配置设计了两个机械上不同的Ti-Mesh支架，以最大程度地减少应力屏蔽，同时确保抵抗机械故障。支架刚度仅通过支柱直径的微小变化而改变。对齐蜂窝以形成三个不同方向的通道（轴向，垂直和倾斜），以引导骨骼再生过程。柔软的支架（0.84 GPa的刚度）和3.5倍的刚性支架（2。在绵羊体内以临界大小的骨缺损模型测试了88 GPa）。为了验证局部支架的刚度可以促进愈合，使用允许动态加载4 cm缺损的普通锁定加压板或机械屏蔽缺损的刚性定制板来稳定缺损。较低的应力屏蔽导致较早的缺损桥接，软骨内骨形成增加以及关键尺寸缺损的早期骨再生。这项研究表明，在翻译的大型动物研究中，对3D添加剂制造的Ti-Mesh支架的力学生物学优化可以增强骨骼的再生。可以使用允许动态加载4厘米缺陷的普通锁定压缩板或可以机械地屏蔽缺陷的刚性定制板来稳定缺陷。较低的应力屏蔽导致较早的缺损桥接，软骨内骨形成增加以及关键尺寸缺损的早期骨再生。这项研究表明，在翻译的大型动物研究中，对3D添加剂制造的Ti-Mesh支架的力学生物学优化可以增强骨骼的再生。可以使用允许动态加载4厘米缺陷的普通锁定压缩板或可以机械地屏蔽缺陷的刚性定制板来稳定缺陷。较低的应力屏蔽导致较早的缺损桥接，软骨内骨形成增加以及关键尺寸缺损的早期骨再生。这项研究表明，在翻译的大型动物研究中，对3D添加剂制造的Ti-Mesh支架的力学生物学优化可以增强骨骼的再生。