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Skin light scattering restricts optical imaging and therapeutic efficacy in deeper layers. Hyaluronic acid (HA) can improve skin optical clearing (OCE), but its influencing factors and mechanisms remain unclear. In ex vivo experiments, mouse and porcine skin models were used to assess the effects of HA with different molecular weights (4 kDa, 28-30 kDa, and 90 kDa) and concentrations (100, 200, and 300 mg/ml) on skin optical clearing. We found that higher molecular weights and concentrations of HA resulted in enhanced skin OCE. Moreover, small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) revealed that HA promotes a more ordered, compact fibril arrangement and reduces collagen fibril diameter. Additionally, HA exhibited good biocompatibility to HaCaT and 3T3-L1 cells. In vivo experiments showed that the skin maximum OCE was reached 30 min after intradermal injection of HA (4 kDa, 300 mg/ml) in mice, accompanied by dermal thinning, decreased fibril diameters, and a more organized fibril structure. This study identifies molecular weight and concentration as key factors influencing HA-induced skin OCE, highlighting its effects on collagen structure and establishing HA as a safe and effective optical clearing agent (OCA) for improving clinical optical imaging and therapy.
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Liu et al. (2025) studied this question.
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