In vivo quantification of hydrogen gas concentration in bone marrow surrounding magnesium fracture fixation hardware using an electrochemical hydrogen gas sensor

Magnesium (Mg) medical devices are currently being marketed for orthopedic applications and have a complex degradation process which includes the evolution of hydrogen gas (H-2). The effect of H-2 exposure on relevant cell types has not been studied; and the concentration surrounding degrading Mg devices has not been quantified to enable such mechanistic studies. A simple and effective method to measure the concentration of H-2 in varying microenvironments surrounding Mg implants is the first step to understanding the biological impact of H-2 on these cells. Here, the in vivo measurement of H-2 surrounding fracture fixation devices implanted in vivo is demonstrated. An electrochemical H-2 microsensor detected increased levels of H-2 at three anatomical sites with a response time of about 30 s. The sensor showed the H-2 concentration in the bone marrow at 1 week post-implantation (1460 +/- 320 mu M) to be much higher than measured in the subcutaneous tissue (550 +/- 210 mu M) and at the skin surface (120 +/- 50 mu M). Additionally, the H-2 concentrations measured in the bone marrow exceeded the concentration in a H-2 saturated water solution (similar to 800 mu M). These results suggest that H-2 emanating from Mg implants in bone during degradation pass through the bone marrow and become at least partially trapped because of slow permeation through the bone. This study is the first to identify H-2 concentrations in the bone marrow environment and will enable in vitro experiments to be executed at clinically relevant H-2 concentrations to explore possible biological effects of H-2 exposure. Statement of Significance An electrochemical H-2 sensor was used to monitor the degradation of a Mg fracture fixation system in a lapine ulna fracture model. Interestingly, the H-2 concentration in the bone marrow is 82% higher than H-2 saturated water solution. This suggests H-2 generated in situ is trapped in the bone marrow and bone is less permeable than the surrounding tissues. The detectable H-2 at the rabbit skin also demonstrates a H-2 sensor's ability to monitor the degradation process under thin layers of tissue. H-2 sensing shows promise as a tool for monitoring the degradation of Mg alloy in vivo and creating in vitro test beds to more mechanistically evaluate the effects of varying H-2 concentrations on cell types relevant to osteogenesis. (C) 2018 Published by Elsevier Ltd on behalf of Acta Materialia Inc.