Yu Dongmei, Tang Zhen, Bao Shusen, Guo Shuo, Chen Changchen, Wu Qi, Wang Mo, Zheng Zenghui, Cao Pengfei, Xu Bin, Wu Hao, Wang Ning, Huang Hai, Liu Chaozong, Li Xiaokang, Guo Zheng
Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Institute of Orthopaedic and Musculoskeletal Science, University College London, Royal National Orthopaedic Hospital, Stanmore, London, HA7 4LP, UK.
Adv Healthc Mater. 2025 Apr;14(9):e2404647. doi: 10.1002/adhm.202404647. Epub 2025 Feb 24.
Up to now, how to implement the optimal regenerative repair of large load-bearing bone defects using artificial bone prosthesis remains to be an enormous challenge in clinical practice. Titanium-based alloys, especially Ti6Al4V, are applied as artificial bone grafts due to their favorable mechanical property and biocompatibility, assisted by personalized customization of 3D-printing to completely match with the bone defect. However, their bioinert peculiarity restricts osteointegration at the interface between bone and titanium-based implants and bone growth into porous titanium-based scaffolds, for lack of bone regeneration with the aid of blood vessels and neural networks. Of note, ample blood delivery and integral innervation are pivotal to the survival of artificially tissue-engineered bones. Herein, the functionalized surface of 3D printed titanium alloy scaffolds driven immunoregulatory neuro-vascularized osseointegration is delved. Bone-like micro/nano morphology and chemical composition of calcium-rich formula are scrutinized to accelerate the process of bone defect repair, including inflammatory response, angiogenesis, neurogenesis, and osseointegration. Micro/nano-topographic calcium titanate (CaTiO) coating, especially 10%HO-Ca, driven immunoregulatory neuro-vascularized osseointegration is validated and its underlying mechanism is attributed to the signaling pathway of TNF-α /oxidative phosphorylation, providing an effective tactic of the bone tissue-engineered scaffold with surface functionalization-driven immunoregulatory neuro-vascularized osseointegration for clinical large segmental bone defects.
到目前为止，如何使用人工骨假体实现大承重骨缺损的最佳再生修复在临床实践中仍然是一个巨大的挑战。钛基合金，尤其是Ti6Al4V，因其良好的机械性能和生物相容性而被用作人工骨移植材料，并借助3D打印的个性化定制使其与骨缺损完全匹配。然而，它们的生物惰性特性限制了骨与钛基植入物界面处的骨整合以及骨向多孔钛基支架内的生长，因为缺乏血管和神经网络辅助的骨再生。值得注意的是，充足的血液供应和完整的神经支配对于人工组织工程骨的存活至关重要。在此，深入研究了3D打印钛合金支架功能化表面驱动的免疫调节性神经血管化骨整合。研究了富含钙配方的类骨微/纳米形态和化学成分，以加速骨缺损修复过程，包括炎症反应、血管生成、神经发生和骨整合。验证了微/纳米拓扑结构的钛酸钙（CaTiO）涂层，尤其是10%HO-Ca涂层驱动的免疫调节性神经血管化骨整合，其潜在机制归因于TNF-α/氧化磷酸化信号通路，为临床大段骨缺损提供了一种具有表面功能化驱动的免疫调节性神经血管化骨整合的骨组织工程支架的有效策略。
