In vivo assessment of collagen transdermal absorption in murine and human skin using photoacoustics microscopy

The therapeutic potential of collagen for transdermal applications has been hindered by its limited penetration efficiency due to its high molecular weight. This study systematically evaluates the transdermal behavior of C3-modified collagen (ICG-C3) in murine, rat, and human skin using photoacoustic imaging (PAI). Dynamic PAI monitoring revealed that ICG-C3 exhibited enhanced penetration (3-fold higher dermal signal intensity than free ICG, P < 0.05) and prolonged retention (a 181.6% longer half-life than unmodified collagen, P < 0.001) in animal models. Human trials further demonstrated that the efficacy of ICG-C3 was dependent on the anatomical site: it achieved a penetration depth of 210 ± 30 μm (P < 0.01) in dorsal skin (characterized by a thick stratum corneum) and it exhibited a reduced signal decay rate to -25% of controls (P < 0.05) in ventral skin (with high sweat gland density). Non-destructive PAI visualized the directional migration of ICG-C3 along skin appendages. Our findings validate the cross-species universality of C3 modification and establish PAI as a robust tool for real-time transdermal analysis, offering critical insights for developing collagen-based therapeutics and advancing photoacoustic imaging in biomedical research.