Dual optical elastography detects TGF-β-induced alterations in the biomechanical properties of skin scaffolds

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta (TGF-β) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF-β, a signaling molecule with diverse cellular functions. Approach: The TGF-β receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF-β. Skin scaffold samples, grouped into three categories (control, TGF-β-treated, and TGF-β + galunisertibtreated), were prepared in two distinct culture media.one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results: Results showed significantly higher wave speed (with AP, p < 0.001; without AP, p < 0.001) and Brillouin frequency shift (with AP, p < 0.001; without AP, p . 0.01) in TGF-β-treated group compared with the control group. The difference in wave speed between the control and TGF-β + galunisertib with (p = 0.10) and without AP (p = 0.36) was not significant. Moreover, the TGF-β + galunisertibtreated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF-β-treated group without AP, further strengthening the potential role of TGF-β in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF-β-induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis.