Titanium surface interacting with clot network and entrapped blood components promotes migration and osteogenic differentiation of bone marrow mesenchymal stem cells

Abstract

Background: A series of biological events was initiated upon the implantation placement, beginning with blood-material contact, followed by coagulation cascade, blood clot formation and bone marrow mesenchymal stromal cells (BMSCs) recruitment. Aim/Hypothesis: The aim of this study was to investigate the effect of implant surface on blood-material interactions and subsequent rBMSCs cellular behaviors via mimicking physiological process in vitro and in vivo. Materials and Methods: This study established in vivo and in vitro to imitate the physiological process of implantation. Titanium slices with sandblasted and double acid-etching (SLA) surface, while polished titanium (PT) surfaces as control group, were incubated with whole blood for 10 min or 2 h, then rBMSCs were seeded. The adhesion, proliferation, migration and differentiation of rBMSCs were studied at specific time points. Titanium implants with different surfaces were implanted into the tibia of Sprague-Dawley (SD) rats and were screwed out at 10 min or 2 h after implantation. The activation of coagulation cascade, platelets and complement system and the clot networks were observed and further quantitatively analyzed. Results: Compared with PT surface, the SLA surface induced the greater and earlier surface-induced blood coagulation cascade and showed more stratified clots network with adsorption of fibrinogen, platelets and CD14 positive cell. Furthermore, increased rBMSCs proliferation as well as the migration and movement of cells were induced by titanium surface pre-incubated with whole blood. Finally, the higher expression levels of the osteogenic-related and angiogenic-related genes showed on SLA surfaces with blood incubation. Conclusions and Clinical Implications: SLA titanium surfaces positively influenced the formed clot structure with entrapped blood components, blood-surface interactions and subsequent cellular biological processes which are important for early bone healing and integration. Acknowledgements: This study was financially supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LY17H40006, National Natural Science Foundation of China (No. 31670970) and Key Research and Development Program of Science and Technology Department of Zhejiang Province (No. 2019C03081). Keywords: Dental implants, Blood incubation, Bone marrow mesenchymal stromal cells, Osteogenesis