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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. [ABSTRACT FROM AUTHOR]

Significance: Recent generation of bioengineered human skin allowed the efficient treatment of patients with severe skin defects. However, the optical and biomechanical properties of these models are not known. Aim: Three models of bioengineered human skin based on fibrin-agarose biomaterials (acellular, dermal skin substitutes, and complete dermoepidermal skin substitutes) were generated and analyzed. Approach: Optical and biomechanical properties of these artificial human skin substitutes were investigated using the inverse adding-doubling method and tensile tests, respectively. Results: The analysis of the optical properties revealed that the model that most resembled the optical behavior of the native human skin in terms of absorption and scattering properties was the dermoepidermal human skin substitutes after 7 to 14 days in culture. The time-course evaluation of the biomechanical parameters showed that the dermoepidermal substitutes displayed significant higher values than acellular and dermal skin substitutes for all parameters analyzed and did not differ from the control skin for traction deformation, stress, and strain at fracture break. Conclusions: We demonstrate the crucial role of the cells from a physical point of view, confirming that a bioengineered dermoepidermal human skin substitute based on fibrin-agarose biomaterials is able to fulfill the minimal requirements for skin transplants for future clinical use at early stages of in vitro development. [ABSTRACT FROM AUTHOR]