Advancing bone implant engineering offers the opportunity to overcome crucial medical challenges and improve clinical outcomes. Although the establishment of a functional vascular network is crucial for bone development, its regeneration inside bone tissue has only received limited attention to date. Herein, we utilize siRNA-decorated particles to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. Specifically, an siRNA was designed to target the regulation of cathepsin K and conjugated on nanoparticles. The functionalized nanoparticles were assembled onto the bone implant to form a hierarchical nanostructured coating. By regulating mRNA transcription, the coating significantly promotes cell viability and growth factor release related to vascularization. Moreover, microchip-based experiments demonstrate that the nanostructured coating facilitates macrophage-induced synergy in up-regulation of at least seven bone and vascular growth factors. Ovariectomized rat and comprehensive beagle dog models highlight that this siRNA-integrated nanostructured coating possesses all the key traits of a clinically promising candidate to address the myriad of challenges associated with bone regeneration.

中文翻译：

---

纳米结构涂层的分层组装，用于基于siRNA的骨再生和血运重建双重治疗。

先进的骨植入技术为克服重大医学难题和改善临床结果提供了机会。尽管功能性血管网络的建立对于骨骼发育至关重要，但迄今为止，其在骨骼组织内部的再生仅受到了有限的关注。在本文中，我们利用siRNA修饰的颗粒在临床使用的钛植入物上设计出层次化的纳米结构涂层，以实现骨骼和血管组织的协同再生。具体而言，将siRNA设计为靶向组织蛋白酶K的调控并偶联在纳米颗粒上。将功能化的纳米颗粒组装到骨植入物上以形成分层的纳米结构涂层。通过调节mRNA转录，涂层显着促进与血管形成有关的细胞活力和生长因子的释放。此外，基于微芯片的实验表明，纳米结构涂层在至少七个骨和血管生长因子的上调中促进了巨噬细胞诱导的协同作用。去卵巢大鼠和全面的比格犬模型强调，这种siRNA整合的纳米结构涂层具有临床上有希望的候选者的所有关键特征，以应对与骨骼再生相关的众多挑战。