Background: Regulating excessive inflammation and oxidative stress in fat grafting may improve retention rates. Hydrogen effectively combats oxidative stress and inflammation and reportedly inhibits ischemia-reperfusion injury in various organs. Unfortunately, with conventional methods of hydrogen administration, incorporating hydrogen continuously into the body over a long period of time is difficult. We hypothesized that a Silicon (Si)-based agent we recently developed would aid in fat grafting as it can generate large amounts of hydrogen continuously in the body. Methods: Fat grafting was performed on the backs of rats fed either a normal or 1.0 wt% Si-based agent-containing diet. To investigate synergistic effects with adipose-derived stromal cells (ASCs), which improve retention rates of fat grafting, fat grafting with ASCs (1.0×10 5/400 mg fat) was also performed in each rat. Postoperative retention rates of grafted fat over time, inflammatory indices, apoptosis and oxidative stress markers, histological findings, and expression levels of inflammation-related cytokines and growth factors were compared between the four groups. Results: Intake of Si-based agent and addition of ASCs significantly reduced inflammatory indices, oxidative stress, and apoptosis of grafted fat, and improved long-term retention rates, histological parameters, and grafted fat quality. Under our experimental conditions, intake of the Si-based agent and addition of ASCs yielded comparable improvements in fat graft retention. Combining the two enhanced these effects even further. Conclusion: Oral administration of the hydrogen-generating Si-based agent may improve grafted fat retention by regulating the inflammatory response and oxidative stress in grafted fat. Clinical relevance statement: This study demonstrates improved grafted fat retention rates using a Si-based agent. This Si-based agent has the potential to expand the range of therapeutic indications of hydrogen-based therapy to conditions for which hydrogen has yet to be found effective, such as fat grafting.
Hydrogen is effective against ischemia-reperfusion (I/R) injury in skin flaps. However, the difficulty of continuously administering a sufficient amount of hydrogen using conventional methods has been an issue in the clinical application of hydrogen-based therapy. An Si-based agent administered orally was previously shown to continuously generate a large amount of hydrogen in the intestinal environment. In this study, we assessed the effect of the Si-based agent on the inhibition of I/R injury in skin flaps using a rat model. In the I/R groups, the vascular pedicle of the abdominal skin flap was occluded for three hours followed by reperfusion. In the I/R + Si group, the Si-based agent was administered perioperatively. After reperfusion, flap survival rate, blood flow, oxidative stress markers, inflammatory markers/findings, and degree of apoptosis were evaluated. Flap survival rate was significantly higher, and histological inflammation, apoptotic cells, oxidative stress markers, and levels of inflammatory cytokine mRNA and protein expression were significantly lower, in the I/R + Si group compared to the I/R group. The Si-based agent suppressed oxidative stress, apoptosis, and inflammatory reactions resulting from I/R injury, thereby contributing to improvements in skin flap survival.