Sugar-Induced Skin Optical Clearing: From Molecular Dynamics Simulation to Experimental Demonstration

The tissue optical clearing technique can significantly improve the quality of biomedical optical imaging. Previous investigations demonstrated that alcohols are excellent optical clearing agents for in vitro skin because they have hydroxyl. However, sugars with hydroxyl groups have received little attention. Here, three sugars, fructose, glucose, and ribose, were investigated using a molecular dynamics simulation and in vitro experiments. The simulated results revealed that fructose and ribose have the highest and lowest optical clearing potential, respectively, according to their propensity to form hydrogen bonds and bridges. The resolutions through skin samples after 24 min of immersion in fructose, glucose, or ribose solutions were quantitatively calculated using a USAF target and reached 14.3 ± 1.2 μm, 27.3 ± 2.4 μm, and 39.6 ± 4.1 μm, respectively, which are in accordance with the theoretical prediction. Unfortunately, topical fructose treatment of in vivo rat skin could not induce excellent optical clearing. Thus, a chemical penetration enhancer was used for in vivo studies. A comparison of laser speckle imaging of dermal blood flow after topical treatment with fructose, a penetration enhancer, and a mixture of the two to rat skin in vivo demonstrated that the mixture causes the largest increase in the resolution and contrast.