Investigation of the biocompatibility of cell-loaded nickel titanium under dynamic mechanical loading

Abstract

Introduction: NiTi-SMA are of increasing biomedical interest due to an unusual pseudo-elasticity and the shape memory effect. However, the high nickel content of NiTi-SMA may result in adverse tissue reactions especially with long-term implants under mechanical strain. It was reported that mechanical strain resulted in nickel ion release from NiTi-wires. NiTi is currently analyzed as carrier material for human mesenchymal stem cells (hMSCs). HMSCs are the most promising cell type for regenerative medicine and tissue engineering due to their ability to differentiate into several tissues such as bone, cartilage, tendon or muscle. For the treatment of local bone defects expanded hMSCs may be applied, loaded on a NiTi carrier matrix. Methods: In order to analyze biocompatibility of mechanically strained NiTi-SMA tensile specimens were preloaded with hMSCs. The specimens were transferred to a sterile PTFE cell culture tube equipped with a cell culture circulation system and fixed to the pull rods of the tensile testing machine. The cell culture tube was located into a conventional cell culture incubator located within the tensile testing machine. 86,400 strain cycles were performed for a period of 24 h and 7 d. Subsequently, the cell culture tube was transferred to the laboratory. The cell culture medium from the tube was aspirated and stored at −80°C. Interleukin-6 (IL-6) and nickel ion release were determined within the circulated cell culture medium. Adherent cells on the tensile specimen were stained by calcein-AM and propidium iodine to analyze cell viability. Results: Dynamic loading did not influence the viability of hMSCs after 24 h or 7 d compared to the non-strained control. Dynamic cycles of loading and unloading increased the nickel ion release from the tensile specimen. It increased from four to five μg/L. The release of IL-6 from hMSCs cultured under dynamic conditions was significantly higher after mechanical load (873 pg/mL) compared to static conditions (323 pg/mL). Conclusion: The presented experimental approach will provide information on the biocompatibility and fatigue behavior of metallic specimens using sample size and dynamic strain relevant for orthopedic implants.