Tyrosinase (TYR) functions as the critical enzyme in biosynthesis of melanin , and its abnormality is an important hallmark for skin pigmentary disorders. This renders the visualization of tyrosinase dynamics a strategically vital way to facilitate clinical diagnostic and monitoring. However, the use of small molecule fluorescent probes to assess tyrosinase levels and evaluate related therapeutics and drugs has been limited. This is mainly due to the aggregation-induced quenching (ACQ) effects of existing fluorescent probes. In this study, we introduce the first aggregation-induced emission (AIE) small molecule fluorescent probe , BTFTYR , for simple, highly sensitive, and effective detection of tyrosinase activity. The specific fluorescence signal generated by tyrosinase catalytic reaction enables the imaging of pigment cells. We demonstrate its application in visualizing tyrosinase with high contrast in living vertebrates, benefiting from the inherent photobleaching resistance of AIE materials, large Stokes shift , and considerable tissue permeability. We also show the outstanding skin penetration capability of BTFTYR in a skin model. Moreover, we present the first comprehensive evaluation of relevant clinical therapeutic approaches or drugs, including ultraviolet B (UVB) irradiation, kojic acid , and α-MSH, by interpreting the tyrosinase variation with BTFTYR . Finally, our studies confirm that BTFTYR neither causes skin inflammation nor produces visceral toxicity, making it a promising chemical tool for medical diagnosis and drug screening. This tool may further help elucidate the pathomechanisms associated with tyrosinase.
The shortage of transplantable skin is the leading cause of death in patients with extensive skin defect. Addressing this challenge urgently requires the development of skin substitutes capable of wound repair and facilitating skin regeneration. In this study, a biomimetic bilayer skin tissue model consisting of collagen, gelatin/sodium alginate, fibroblasts, human umbilical vein endothelial cells, keratinocytes, melanocytes, and verteporfin was devised. Then, the skin model was fabricated using precise extrusion/inkjet bioprinters, and it reconstruction capabilities were evaluated through skin defect repair experiments. The printed skin tissue reduced the inflammatory response of the wound by 38% and inhibited the expression of TGF-β and YAP, and promoted the transformation of macrophages from M1 phenotype to M2 phenotype, thus promoting the reasonable reconstruction of fibronectin and collagen on the wound, finally promoting the wound healing, and reducing the wound contraction and scar formation. In addition, the proliferation and differentiation of human umbilical vein endothelial cells, keratinocytes, and melanocytes in printed skin increased the number of regenerated blood vessels by 123%, while promoting the reconstruction of multilayer epidermal structure and skin color. The outcomes of this investigation present a promising skin model and therapeutic strategy for skin injury, offering a potential avenue for the reconstruction of skin structure and function.
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