Dual optical elastography detects TGF - ß -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 - ß ) 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 - ß , a signaling molecule with diverse cellular functions. Approach: The TGF - ß receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF - ß . Skin scaffold samples, grouped into three categories (control, TGF - ß -treated, and TGF - ß + galunisertib-treated), 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 - ß -treated group compared with the control group. The difference in wave speed between the control and TGF - ß + galunisertib with ( p = 0.10 ) and without AP ( p = 0.36 ) was not significant. Moreover, the TGF - ß + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF - ß -treated group without AP, further strengthening the potential role of TGF - ß in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF - ß -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.

Dolutegravir induces FOLR1 expression during brain organoid development.

During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.