Zhang Jiaxin, Bai Haotian, Liu He, Wang Xiaonan, Xu Mingwei, Zhang Guokun, Di Zexin, Zhao Xin, Wang Jincheng, Ren Luquan
Orthopedic Institute of Jilin Province, Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, 130041, PR China.
Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, 130041, PR China.
J Orthop Translat. 2025 Apr 5;51:360-378. doi: 10.1016/j.jot.2025.01.009. eCollection 2025 Mar.
Imbalances in the osteogenic-osteoclastic microenvironment hinder effective osseointegration between the prosthesis and host bone, which is a key factor contributing to the high incidence of prosthesis loosening and periprosthetic fractures in osteoporosis patients. Developing an implant interface that can reverse the dysregulated osteogenic microenvironment is an effective strategy to address this challenge.
A novel bioinspired interface with a spatial gradient structure was engineered by 3D-printed porous titanium alloy implants and hollow mesoporous silica nanoparticles coating. Apart from the bioinspired bone microstructure, the amine-functionalized nanocoating of the bioactive interface could also load and temporally sustain the zoledronic acid (ZOL) release. A series of experiments were carried out to characterize the bioactive interface and to clarify the regulation of osteogenic-osteoclastic balance by ZOL temporal release from the nanocoatings. Afterward, an osteoporotic model was utilized to validate the bioactive interface osseointegration effect.
Based on the structural features and chemical properties of the bioactive interface, efficient ZOL loading was achieved. Additionally, the temporal release mechanism of ZOL through free diffusion and ionic bond ionization enabled long-term sustained release. Meanwhile, the early high-concentration local release of ZOL effectively inhibited osteoclast formation and activation in the microenvironment. As the ZOL release decreased over time, the focus shifted to promoting the process of bone formation, thereby reversing the dysregulated osteogenic microenvironment. According to this, we identified the optimal gradient concentration (10M) of the ZOL temporal release system that efficiently exerts bidirectional regulatory effects. Most notably, the spatial gradient structured interface loaded with this optimal concentration of ZOL (10M) significantly augmented osseointegration under osteoporotic conditions.
Overall, our study provides a novel nanocoating capable of temporally releasing ZOL to reverse the dysregulated osteogenic microenvironment, aiming to maintain the long-term stability of artificial prostheses for osteoporosis patients.
This study validates the structure-performance-effect relationship of ZOL-releasing nanocoatings with a temporal release mechanism, providing a novel approach to addressing the high incidence of postoperative complications in osteoporotic patients undergoing prosthetic replacement.
成骨-破骨微环境失衡阻碍了假体与宿主骨之间有效的骨整合，这是导致骨质疏松患者假体松动和假体周围骨折高发的关键因素。开发一种能够逆转失调的成骨微环境的植入物界面是应对这一挑战的有效策略。
通过3D打印多孔钛合金植入物和中空介孔二氧化硅纳米颗粒涂层设计了一种具有空间梯度结构的新型仿生界面。除了仿生骨微结构外，生物活性界面的胺功能化纳米涂层还可以负载并暂时维持唑来膦酸（ZOL）的释放。进行了一系列实验来表征生物活性界面，并阐明纳米涂层中ZOL的时间释放对成骨-破骨平衡的调节作用。之后，利用骨质疏松模型验证生物活性界面的骨整合效果。
基于生物活性界面的结构特征和化学性质，实现了ZOL的高效负载。此外，ZOL通过自由扩散和离子键电离的时间释放机制实现了长期持续释放。同时，ZOL早期的高浓度局部释放在微环境中有效抑制了破骨细胞的形成和激活。随着ZOL释放量随时间减少，重点转向促进骨形成过程，从而逆转失调的成骨微环境。据此，我们确定了能有效发挥双向调节作用的ZOL时间释放系统的最佳梯度浓度（10M）。最值得注意的是，负载此最佳浓度ZOL（10M）的空间梯度结构界面在骨质疏松条件下显著增强了骨整合。
总体而言，我们的研究提供了一种能够暂时释放ZOL以逆转失调的成骨微环境的新型纳米涂层，旨在维持骨质疏松患者人工假体的长期稳定性。
本研究验证了具有时间释放机制的ZOL释放纳米涂层的结构-性能-效应关系，为解决接受假体置换的骨质疏松患者术后并发症高发问题提供了一种新方法。
