Sheng Wang,1,* Demeng Xia,2,3,* Wenxue Dou,4,* Aimin Chen,1 Shuogui Xu2 

1Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Traumatic Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Clinical Medicine, Hainan Health Vocational College, Haikou, 570100, People’s Republic of China; 4Department of Stomatology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Shuogui Xu, Department of Emergency, Changhai Hospital, Naval Medical University, Xiangyin Road, Shanghai, 200433, People’s Republic of China, Email 18516116672@163.com Aimin Chen, Department of traumatic orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China, Email chenaimin2023@163.com

Background: Delayed healing and non-healing of bone defects pose significant challenges in clinical practice, with metal materials increasingly recognized for their significance in addressing these issues. Among these materials, Strontium (Sr) and Zinc (Zn) have emerged as promising agents for promoting bone repair. Building upon this insight, this research evaluates the impact of a porous Sr@Zn@SiO2 nanocomposite implant on bone regeneration, aiming to advance the field of bone repair.
Methods: The preparation of the Sr@Zn@SiO2 composite implant involves various techniques such as roasting, centrifugation, and washing. The material’s composition is examined, and its microstructure and element distribution are analyzed using TEM and elemental scanning technology. In vitro experiments entail the isolation and characterization of BMSCs followed by safety assessments of the implant material, evaluation of cell migration capabilities, and relevant proliferation markers. Mechanistically, this study delves into key targets associated with significant changes in the osteogenic process. In vivo experiments involve establishing a rat femur bone defect model, followed by assessment of the osteogenic potential of Sr@Zn@SiO2 using Micro-CT imaging and tissue section staining.
Results: Through in vivo and in vitro investigations, we validate the osteogenic efficacy of the Sr@Zn@SiO2 composite implant. In vitro analyses demonstrate that porous Sr@Zn@SiO2 nanocomposite materials upregulate BMP-2 expression, leading to the activation of Smad1/5/9 phosphorylation and subsequent activation of downstream osteogenic genes, culminating in BMSCs osteogenic differentiation and bone proliferation. And the migration of BMSCs is closely related to the high expression of CXCL12/CXCR4, which will also provide the conditions for osteogenesis. In vivo, the osteogenic ability of Sr@Zn@SiO2 was also confirmed in rats.
Conclusion: In our research, the porous Sr@Zn@SiO2 composite implant displays prominent osteogenic effect and promotes the migration and differentiation of BMSCs to promote bone defect healing. This bioactive implant has surgical application potential in the future.

Keywords: bioactive porous composite, differentiation and migration, bone reconstruction, smad1/5/9